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DRUG APPROVALS BY DR ANTHONY MELVIN CRASTO .....FOR BLOG HOME CLICK HERE

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ORGANIC SPECTROSCOPY

Read all about Organic Spectroscopy on ORGANIC SPECTROSCOPY INTERNATIONAL 

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DR ANTHONY MELVIN CRASTO Ph.D

DR ANTHONY MELVIN CRASTO Ph.D

DR ANTHONY MELVIN CRASTO, Born in Mumbai in 1964 and graduated from Mumbai University, Completed his Ph.D from ICT, 1991,Matunga, Mumbai, India, in Organic Chemistry, The thesis topic was Synthesis of Novel Pyrethroid Analogues, Currently he is working with GLENMARK PHARMACEUTICALS LTD, Research Centre as Principal Scientist, Process Research (bulk actives) at Mahape, Navi Mumbai, India. Total Industry exp 30 plus yrs, Prior to joining Glenmark, he has worked with major multinationals like Hoechst Marion Roussel, now Sanofi, Searle India Ltd, now RPG lifesciences, etc. He has worked with notable scientists like Dr K Nagarajan, Dr Ralph Stapel, Prof S Seshadri, Dr T.V. Radhakrishnan and Dr B. K. Kulkarni, etc, He did custom synthesis for major multinationals in his career like BASF, Novartis, Sanofi, etc., He has worked in Discovery, Natural products, Bulk drugs, Generics, Intermediates, Fine chemicals, Neutraceuticals, GMP, Scaleups, etc, he is now helping millions, has 9 million plus hits on Google on all Organic chemistry websites. His friends call him Open superstar worlddrugtracker. His New Drug Approvals, Green Chemistry International, All about drugs, Eurekamoments, Organic spectroscopy international, etc in organic chemistry are some most read blogs He has hands on experience in initiation and developing novel routes for drug molecules and implementation them on commercial scale over a 30 year tenure till date Dec 2017, Around 35 plus products in his career. He has good knowledge of IPM, GMP, Regulatory aspects, he has several International patents published worldwide . He has good proficiency in Technology transfer, Spectroscopy, Stereochemistry, Synthesis, Polymorphism etc., He suffered a paralytic stroke/ Acute Transverse mylitis in Dec 2007 and is 90 %Paralysed, He is bound to a wheelchair, this seems to have injected feul in him to help chemists all around the world, he is more active than before and is pushing boundaries, He has 9 million plus hits on Google, 2.5 lakh plus connections on all networking sites, 50 Lakh plus views on dozen plus blogs, He makes himself available to all, contact him on +91 9323115463, email amcrasto@gmail.com, Twitter, @amcrasto , He lives and will die for his family, 90% paralysis cannot kill his soul., Notably he has 19 lakh plus views on New Drug Approvals Blog in 216 countries......https://newdrugapprovals.wordpress.com/ , He appreciates the help he gets from one and all, Friends, Family, Glenmark, Readers, Wellwishers, Doctors, Drug authorities, His Contacts, Physiotherapist, etc

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Cenegermin


Image result for cenegermin
Active Substance General information The active substance in Oxervate, cenegermin, is a recombinant human Nerve Growth factor (rhNGF) produced in E. coli strain HMS174. The molecule is identical to human Nerve Growth factor (NGF), a naturally occurring human protein. In humans, NGF is naturally produced as pre-pro-peptide, secreted into the endoplasmic reticulum and cleaved by furin protease. The pro-sequence is further cleaved during the production process by enzymatic hydrolysis. Therefore these two amino acid changes have no influence on the final active ingredient (rhNGF), which is identical to the naturally secreted human protein. The 3D structure of rhNGF is a non-covalent dimer with three intra-molecular disulphide bridges. Cenegermin contains 118 amino acids and has a relative molecular mass of 13,266 Daltons and the following molecular formula: C583H908N166O173S8. Figure 1 shows the protein sequence of recombinant human ProNGFrh ProNGF (Figure 1A), and a map of the disulphide bridges (Figure IB):
Cenegermin sequence:
SSSHPIFHRGEFSVCDSVSVWVGDKTTATDIKGKEVMVLGEVNIN
NSVFKQYFFETKCRDPNPVDSGCRGIDSKHWNSYCTTTHTFVKAL
TMDGKQAAWRFIRIDTACVCVLSRKAVR
CAS 1772578-74-1
rhNGF, Nerve growth factor – Anabasis/Dompe; Oxervate; Sentinel
  • OriginatorAnabasis Pharma
  • DeveloperDompe Farmaceutici; Ospedale San Raffaele
  • ClassEye disorder therapies; Nerve growth factors; Neuroprotectants; Proteins
  • Mechanism of ActionNerve growth factor receptor agonists; Neuron stimulants
  • Orphan Drug StatusYes – Keratitis; Retinitis pigmentosa
  • Highest Development Phases
  • RegisteredKeratitis
  • Phase II Dry eyes; Glaucoma; Retinitis pigmentosa
  • APPROVED FDA AUG  2018

Most Recent Events

  • 28 Jul 2018No recent reports of development identified for phase-I development in Glaucoma in Italy (Ophthalmic, Drops)
  • 29 May 2018Phase-II clinical trials in Glaucoma (Ophthalmic) (http://www.dompe.com/RnD-Pipeline/)
  • 01 May 2018Dompé Farmaceutici completes a phase I trial in Glaucoma in USA (Ophthalmic) (NCT02855450)
  • Image result for cenegermin
Cenegermin (planned brand names OxervateSentinel), also known as recombinant human nerve growth factor (rhNGF), is a recombinant form of human nerve growth factor (NGF). It was approved in the European Union as an eye drop formulation for the treatment of moderate or severe neurotrophic keratitis in adults on 6 July 2017.[2][3][1] As a recombinant form of NGF, cenegermin is a peripherally selective agonist of the TrkA and LNGFR (p75NTR) which must be administered parenterally.[3] In addition to neurotrophic keratitis, cenegermin is also under development for the treatment of dry eyesretinitis pigmentosa, and glaucoma.[3] It was developed by Anabasis Pharma, Dompé Farmaceutici, and Ospedale San Raffaele.[3]
Cenegermin is a human beta-nerve growth factor (beta-ngf)-(1-118)- peptide (non-covalent dimer) produced in escherichia coli. It received European Union Approval in July, 2017 for the treatment of moderate to severe neurotrophic keratitis.
In 2013, orphan drug designations in the E.U. and in the U.S. were assigned to the candidate for the treatment of retinitis pigmentosa. The product was granted additional orphan drug designation for the treatment of neurotrophic keratitis in the U.S. and the E.U. in 2014 and 2015, respectively.
Cenegermin, a recombinant human nerve growth factor developed by Dompé was first approved in July 2017 in the E.U. for the treatment of moderate to severe neurotrophic keratitis (NK) in adults
Clip
The U.S. Food and Drug Administration today approved the first drug, Oxervate (cenegermin), for the treatment of neurotrophic keratitis, a rare disease affecting the cornea (the clear layer that covers the colored portion of the front of the eye).
“While the prevalence of neurotrophic keratitis is low, the impact of this serious condition on an individual patient can be devastating,” said Wiley Chambers, M.D., an ophthalmologist in the FDA’s Center for Drug Evaluation and Research. “In the past, it has often been necessary to turn to surgical interventions; these treatments are usually only palliative in this disease. Today’s approval provides a novel topical treatment and a major advance that offers complete corneal healing for many of these patients.”

August 22, 2018

Release

The U.S. Food and Drug Administration today approved the first drug, Oxervate (cenegermin), for the treatment of neurotrophic keratitis, a rare disease affecting the cornea (the clear layer that covers the colored portion of the front of the eye).

“While the prevalence of neurotrophic keratitis is low, the impact of this serious condition on an individual patient can be devastating,” said Wiley Chambers, M.D., an ophthalmologist in the FDA’s Center for Drug Evaluation and Research. “In the past, it has often been necessary to turn to surgical interventions; these treatments are usually only palliative in this disease. Today’s approval provides a novel topical treatment and a major advance that offers complete corneal healing for many of these patients.”

Neurotrophic keratitis is a degenerative disease resulting from a loss of corneal sensation. The loss of corneal sensation impairs corneal health causing progressive damage to the top layer of the cornea, including corneal thinning, ulceration, and perforation in severe cases. The prevalence of neurotrophic keratitis has been estimated to be less than five in 10,000 individuals.

The safety and efficacy of Oxervate, a topical eye drop containing cenegermin, was studied in a total of 151 patients with neurotrophic keratitis in two, eight-week, randomized controlled multi-center, double-masked studies. In the first study, patients were randomized into three different groups. One group received Oxervate, a second group received an eye drop with a different concentration of cenegermin, and the third group received an eye drop without cenegermin. In the second study, patients were randomized into two groups. One group was treated with Oxervate eye drops and the other group was treated with an eye drop without cenegermin. All eye drops in both studies were given six times daily in the affected eye(s) for eight weeks. In the first study, only patients with the disease in one eye were enrolled, while in the second study, patients with the disease in both eyes were treated in both eyes (bilaterally). Across both studies, complete corneal healing in eight weeks was demonstrated in 70 percent of patients treated with Oxervate compared to 28 percent of patients treated without cenegermin (the active ingredient in Oxervate).

The most common adverse reactions in patients taking Oxervate are eye pain, ocular hyperemia (enlarged blood vessels in the white of the eyes), eye inflammation and increased lacrimation (watery eyes).

Oxervate was granted Priority Review designation, under which the FDA’s goal is to take action on an application within six months of application filing where the agency determines that the drug, if approved, would provide a significant improvement in the safety or effectiveness of the treatment, diagnosis or prevention of a serious condition. Oxervate also received Orphan Drug designation, which provides incentives to assist and encourage the development of drugs for rare diseases.

The FDA granted approval of Oxervate to Dompé farmaceutici SpA.

Cenegermin
Clinical data
Trade names Oxervate, Sentinel
Synonyms Recombinant human nerve growth factor; rhNGF; human beta-nerve growth factor (beta-NGF)-(1-118) peptide (non-covalent dimer) produced in Escherichia coli[1]
Routes of
administration
Eye drops
ATC code
Identifiers
CAS Number
DrugBank
ChemSpider
  • None
UNII
KEGG
Chemical and physical data
Formula C583H908N166O173S8
Molar mass 13266.94 g/mol

References

External links

////////////fda 2018, Oxervate, cenegermin, orphan drug, priority review, EU 2017, DOMPE, neurotrophic keratitis
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Nusinersen sodium, ヌシネルセンナトリウム


ヌシネルセンナトリウム
Nusinersen Sodium

C234H323N61Na17O128P17S17 : 7500.89
[1258984-36-9 , ヌシネルセン]

Nusinersen sodium

C234H323N61O128P17S17.17Na, 7500.8854

UNII 4CHB7QQU1Q

ISIS 396443

Nusinersen sodium was approved by the US Food and Drug Administration (FDA) on Dec 23, 2016, and approved by the European Medicines Agency’s (EMA) on May 30, 2017, and approved by Pharmaceuticals and Medical Devices Agency of Japan (PMDA) on July 3, 2017.

JAPAN APPROVAL

2017/7/3 Nusinersen sodium Spinraza Biogen Japan

An antisense oligonucleotide that induces survival motor neuron (SMN) protein expression, it was approved by the U.S. FDA in December, 2016 as Spinraza for the treatment of children and adults with spinal muscular atrophy (SMA). It is adminstrated as direct intrathecal injection.Nusinersen sodium colored.svg

FREE FORM CAS: 1258984-36-9

Image result for nusinersen

CAS1258984-36-9

MFC234H340N61O128P17S17

ISIS-396443, ISIS-SMNRx, IONIS-SMNRx

RNA, (2′-0-(2-methoxyethyi))(p-thio)(m5u-c-a-c-m5u-m5u-m5u-c-a-m5ua- a-m5 u-g-c-m5u-g-g)

RNA, (2′-0-(2-METHOXYETHYI))(P-THIO)(M5U-C-A-C-M5U-M5U-M5U-C-A-M5UA- A-M5 U-G-C-M5U-G-G)

All-P-ambo-2′-O-(2-methoxyethyl)-5-methyl-P-thiouridylyl-(3’¨5′)-2′-O-(2-methoxyethyl)-5-methyl-P-thiocytidylyl-(3’¨5′)-2′-O-(2-methoxyethyl)-P-thioadenylyl-(3’¨5′)-2′-O-(2-methoxyethyl)-5-methyl-P-thiocytidylyl-(3’¨5′)-2′-O-(2-methoxyethyl)-5-methyl-P-thiouridylyl-(3’¨5′)-2′-O-(2-methoxyethyl)-5-methyl-P-thiouridylyl-(3’¨5′)-2′-O-(2-methoxyethyl)-5-methyl-P-thiouridylyl-(3’¨5′)-2′-O-(2-methoxyethyl)-5-methyl-P-thiocytidylyl-(3’¨5′)-2′-O-(2-methoxyethyl)-P-thioadenylyl-(3’¨5′)-2′-O-(2-methoxyethyl)-5-methyl-P-thiouridylyl-(3’¨5′)-2′-O-(2-methoxyethyl)-P-thioadenylyl-(3’¨5′)-2′-O-(2-methoxyethyl)-P-thioadenylyl-(3’¨5′)-2′-O-(2-methoxyethyl)-5-methyl-P-thiouridylyl-(3’¨5′)-2′-O-(2-methoxyethyl)-P-thioguanylyl-(3’¨5′)-2′-O-(2-methoxyethyl)-5-methyl-P-thiocytidylyl-(3’¨5′)-2′-O-(2-methoxyethyl)-5-methyl-P-thiouridylyl-(3’¨5′)-2′-O-(2-methoxyethyl)-P-thioguanylyl-(3’¨5′)-2′-O-(2-methoxyethyl)guanosine

ISIS-SMNRx is a drug that is designed to modulate the splicing of the SMN2 gene to significantly increase the production of functional SMN protein. The US regulatory agency has granted Orphan Drug Designation with Fast Track Status to nusinersen for the treatment of patients with SMA. The European regulatory agency has granted Orphan Drug Designation to nusinersen for the treatment of patients with SMA.

Nusinersen,[1] marketed as Spinraza,[3] is a medication used in treating spinal muscular atrophy (SMA),[4] a rare neuromuscular disorder. In December 2016, it became the first approved drug used in treating this disorder. Nusinersen has orphan drugdesignation in the United States and the European Union.[5]

Image result for nusinersen

FDA

FDA approves first drug for spinal muscular atrophy

New therapy addresses unmet medical need for rare disease

The U.S. Food and Drug Administration today approved Spinraza (nusinersen), the first drug approved to treat children and adults with spinal muscular atrophy (SMA), a rare and often fatal genetic disease affecting muscle strength and movement. Spinraza is an injection administered into the fluid surrounding the spinal cord.

Read more.

For Immediate Release

December 23, 2016

The U.S. Food and Drug Administration today approved Spinraza (nusinersen), the first drug approved to treat children and adults with spinal muscular atrophy (SMA), a rare and often fatal genetic disease affecting muscle strength and movement. Spinraza is an injection administered into the fluid surrounding the spinal cord.

“There has been a long-standing need for a treatment for spinal muscular atrophy, the most common genetic cause of death in infants, and a disease that can affect people at any stage of life,” said Billy Dunn, M.D., director of the Division of Neurology Products in the FDA’s Center for Drug Evaluation and Research. “As shown by our suggestion to the sponsor to analyze the results of the study earlier than planned, the FDA is committed to assisting with the development and approval of safe and effective drugs for rare diseases and we worked hard to review this application quickly; we could not be more pleased to have the first approved treatment for this debilitating disease.”

SMA is a hereditary disease that causes weakness and muscle wasting because of the loss of lower motor neurons controlling movement. There is wide variability in age of onset, symptoms and rate of progression. Spinraza is approved for use across the range of spinal muscular atrophy patients.

The FDA worked closely with the sponsor during development to help design and implement the analysis upon which this approval was based. The efficacy of Spinraza was demonstrated in a clinical trial in 121 patients with infantile-onset SMA who were diagnosed before 6 months of age and who were less than 7 months old at the time of their first dose. Patients were randomized to receive an injection of Spinraza, into the fluid surrounding the spinal cord, or undergo a mock procedure without drug injection (a skin prick). Twice the number of patients received Spinraza compared to those who underwent the mock procedure. The trial assessed the percentage of patients with improvement in motor milestones, such as head control, sitting, ability to kick in supine position, rolling, crawling, standing and walking.

The FDA asked the sponsor to conduct an interim analysis as a way to evaluate the study results as early as possible; 82 of 121 patients were eligible for this analysis. Forty percent of patients treated with Spinraza achieved improvement in motor milestones as defined in the study, whereas none of the control patients did.

Additional open-label uncontrolled clinical studies were conducted in symptomatic patients who ranged in age from 30 days to 15 years at the time of the first dose, and in presymptomatic patients who ranged in age from 8 days to 42 days at the time of first dose. These studies lacked control groups and therefore were more difficult to interpret than the controlled study, but the findings appeared generally supportive of the clinical efficacy demonstrated in the controlled clinical trial in infantile-onset patients.

The most common side effects found in participants in the clinical trials on Spinraza were upper respiratory infection, lower respiratory infection and constipation. Warnings and precautions include low blood platelet count and toxicity to the kidneys (renal toxicity). Toxicity in the nervous system (neurotoxicity) was observed in animal studies.

The FDA granted this application fast track designation and priority review. The drug also received orphan drug designation, which provides incentives to assist and encourage the development of drugs for rare diseases.

The sponsor is receiving a rare pediatric disease priority review voucher under a program intended to encourage development of new drugs and biologics for the prevention and treatment of rare pediatric diseases. A voucher can be redeemed by a sponsor at a later date to receive priority review of a subsequent marketing application for a different product. This is the eighth rare pediatric disease priority review voucher issued by the FDA since the program began.

Spinraza is marketed by Biogen of Cambridge, Massachusetts and was developed by Ionis Pharmaceuticals of Carlsbad, California.

Medical use

The drug is used to treat spinal muscular atrophy associated with a mutation in the SMN1 gene. It is administered directly to the central nervous system (CNS) using intrathecal injection.[2]

In clinical trials, the drug halted the disease progression. In around 60% of infants affected by type 1 spinal muscular atrophy, the drug also significantly improved motor function.[2]

Image result for Nusinersen sodium

Side effects

Like other antisense drugs, there is a risk of abnormalities in blood clotting and a reduction in platelets as well as a risk of kidney damage.[2]

In clinical trials, people treated with nusinersen had an increased risk of upper and lower respiratory infections and congestion, ear infections, constipation, pulmonary aspiration, teething, and scoliosis. One infant in a clinical trial had severe lowering of salt levels and several had rashes. There is a risk that growth of infants and children might be stunted. In older clinical trial subjects, the most common adverse events were headache, back pain, and adverse effects from the spinal injection.[2]

Some people may develop antibodies against the drug; as of December 2016 it was unclear what effect this might have on efficacy or safety.[2]

Pharmacology

Spinal muscular atrophy is caused by loss-of-function mutations in the SMN1 gene which codes for survival motor neuron (SMN) protein. Patients survive owing to low amounts of the SMN protein produced from the SMN2 gene. Nusinersen modulates alternate splicing of the SMN2 gene, functionally converting it into SMN1 gene, thus increasing the level of SMN protein in the CNS.[6]

The drug distributes to CNS and to peripheral tissues.[2]

The half-life is estimated to be 135 to 177 days in CSF and 63 to 87 days in blood plasma. The drug is metabolized via exonuclease (3’- and 5’)-mediated hydrolysis and does not interact with CYP450 enzymes.[2] The primary route of elimination is likely by urinary excretion for nusinersen and its metabolites.[2]

Chemistry

Nusinersen is an antisense oligonucleotide in which the 2’-hydroxy groups of the ribofuranosyl rings are replaced with 2’-O-2-methoxyethyl groups and the phosphate linkages are replaced with phosphorothioate linkages.[2][6]

History

Nusinersen was discovered in a collaboration between Adrian Krainer at Cold Spring Harbor Laboratory and Ionis Pharmaceuticals (formerly called Isis Pharmaceuticals).[7][8][9][10] Partial work was done at the University of Massachusetts Medical School funded by Cure SMA.[11]

Starting in 2012, Ionis partnered with Biogen on development and in 2015 Biogen acquired an exclusive license to the drug for a US$75 million license fee, milestone payments up to US$150 million, and tiered royalties thereafter; Biogen also paid the costs of development subsequent to taking the license.[12] The license to Biogen included licenses to intellectual property that Ionis had acquired from Cold Spring Harbor Laboratory and University of Massachusetts.[13]

In November 2016, the new drug application was accepted under the FDA’s priority review process on the strength of the Phase III trial and the unmet need, and was also accepted for review at the European Medicines Agency (EMA) at that time.[14][15] It was approved by the FDA in December 2016 and by EMA in May 2017 as the first drug to treat spinal muscular atrophy.[16][17] Subsequently, nusinersen was approved to treat SMA in Canada (July 2017),[18] Japan (July 2017),[19] Brasil (August 2017)[20] and Switzerland (September 2017).[21]

Controversy

Spinraza list price is US$125,000 per injection which puts the treatment cost at US$750,000 in the first year and US$375,000 annually after that. According to the New York Times, this places Spinraza “among the most expensive drugs in the world”.[15]

As of October 2017, Spinraza is reimbursed by health insurance providers in the United States and by the public healthcare systems in France (SMA type 1 and 2 patients only), Germany (all patients), Iceland (all patients), Italy (all patients) and Japan (SMA type 1 only).[3]

In October 2017, the authorities in Denmark recommended Spinraza for use only in a small subset of patients with SMA type 1 (young babies) and refused to offer it as a standard treatment in all other SMA patients quoting an “unreasonably high price” compared to the clinical effect.[22] Norwegian authorities rejected the funding in October 2017 because the price of the medicine was “unethically high”.[23] In February 2018 the funding was approved for patients under 18 years old.[23]

In January 2018 public funding of Spinraza was approved in Israel.

Nusinersen (formerly, IONIS-SMNRx, ISIS-SMNRx), intended to be marketed as Spinraza,[1] is an investigational drug for spinal muscular atrophy developed by Ionis Pharmaceuticals and Biogen with financial support from SMA Foundation and Cure SMA. It is a proprietary antisense oligonucleotide that modulates alternate splicing of the SMN2 gene, functionally converting it into SMN1 gene.

The drug is administered directly to the central nervous system using intrathecal injection once every 3–4 months.

Nusinersen has orphan drug designation in the United States and the European Union.[2]

In August 2016, a phase III trial in type 1 SMA patients was ended early due to positive efficacy data, with Biogen deciding to file for regulatory approval for the drug.[3]Consequently, the company submitted a New Drug Application to the FDA in September 2016[4] and a marketing authorisation application to the European Medicines Agency, under the centralised procedure,[5] in the following month. The company also announced an expanded access programme of nusinersen in type 1 SMA in selected countries.

In November 2016, a phase III clinical trial in type 2 SMA patients was halted after an interim analysis indicated the drug’s efficacy also in this SMA type.[6]

Image result for nusinersen

Image result for nusinersen

Image result for nusinersen

P.S. : The views expressed are my personal and in no-way suggest the views of the professional body or the company that I represent.

References

  1. Jump up to:a b “International Nonproprietary Names for Pharmaceutical Substances (INN). Recommended International Nonproprietary Names: List 74” (PDF). World Health Organization. pp. 413–14. Retrieved 13 March 2017.
  2. Jump up to:a b c d e f g h i j k “Nusinersen US Label” (PDF). FDA. December 2016. For updates see FDA index page for NDA 209531
  3. Jump up to:a b “Nusinersen”. AdisInsight. Retrieved 1 January 2017.
  4. Jump up^ Ottesen, Eric W. (2017-01-01). “ISS-N1 makes the first FDA-approved drug for spinal muscular atrophy”Translational Neuroscience8 (1): 1–6. doi:10.1515/tnsci-2017-0001ISSN 2081-6936PMC 5382937Freely accessiblePMID 28400976.
  5. Jump up^ “Nusinersen”. UK Specialist Pharmacy Service. Retrieved 31 December 2016.
  6. Jump up to:a b Zanetta, C; Nizzardo, M; Simone, C; Monguzzi, E; Bresolin, N; Comi, GP; Corti, S (1 January 2014). “Molecular Therapeutic Strategies for Spinal Muscular Atrophies: Current and Future Clinical Trials”. Clinical Therapeutics36 (1): 128–40. doi:10.1016/j.clinthera.2013.11.006PMID 24360800.
  7. Jump up^ Garber, K (11 October 2016). “Big win possible for Ionis/Biogen antisense drug in muscular atrophy”. Nature Biotechnology34 (10): 1002–1003. doi:10.1038/nbt1016-1002PMID 27727217.
  8. Jump up^ Wadman, Meredith (23 December 2016). “Updated: FDA approves drug that rescues babies with fatal neurodegenerative disease”Science.
  9. Jump up^ Offord, Catherine (December 1, 2016). “Oligonucleotide Therapeutics Near Approval”The Scientist.
  10. Jump up^ Tarr, Peter (24 December 2016). “CSHL FDA approval of life-saving SMA drug is hailed by its researcher-inventor at CSHL”Cold Spring Harbor Laboratory.
  11. Jump up^ “Therapeutic Approaches”http://www.curesma.org. Cure SMA. Retrieved 1 January 2017.
  12. Jump up^ “Biogen Shells Out $75M to Develop Ionis’ Nusinersen after Positive Phase III Results”Genetic Engineering News, August 1, 2016
  13. Jump up^ “Press release: Biogen and Ionis Pharmaceuticals Report Nusinersen Meets Primary Endpoint at Interim Analysis of Phase 3 ENDEAR Study in Infantile-Onset Spinal Muscular Atrophy | Biogen Media”Biogen. August 1, 2016.
  14. Jump up^ “Regulatory Applications for SMA Therapy Nusinersen Accepted in US, EU”. BioNews Services, LLC. Retrieved 2016-11-15.
  15. Jump up to:a b Katie Thomas (December 30, 2016). “Costly Drug for Fatal Muscular Disease Wins F.D.A. Approval”New York Times.
  16. Jump up^ Grant, Charley (2016-12-27). “Surprise Drug Approval Is Holiday Gift for Biogen”Wall Street JournalISSN 0099-9660. Retrieved 2016-12-27.
  17. Jump up^ “Spinraza (nusinersen)”European Medicines Agency. Retrieved 2017-10-27.
  18. Jump up^ “Biogen’s SPINRAZA™ (nusinersen) Receives Notice of Compliance from Health Canada for the Treatment of 5q Spinal Muscular Atrophy (SMA)”Cision. 2017-07-04.
  19. Jump up^ “Biogen to launch Spinraza in Japan soon”. 2017-07-10.
  20. Jump up^ “Remédio inédito para atrofia muscular espinhal é liberado” (in Portuguese). 2017-08-25.
  21. Jump up^ “Spinraza – Zulassung nun auch in der Schweiz” (in German). SMA Schweiz. 2017-09-30.
  22. Jump up^ Medicinrådet siger nej til lægemiddel til børn med muskelsvind: ‘Urimeligt’ dyrt Retrieved October 13 2017.
  23. Jump up to:a b Dette er uforståelig og utrolig urettferdig

Further reading

  • Finkel, Richard S; Chiriboga, Claudia A; Vajsar, Jiri; Day, John W; Montes, Jacqueline; De Vivo, Darryl C; Yamashita, Mason; Rigo, Frank; Hung, Gene; Schneider, Eugene; Norris, Daniel A; Xia, Shuting; Bennett, C Frank; Bishop, Kathie M (2016). “Treatment of infantile-onset spinal muscular atrophy with nusinersen: A phase 2, open-label, dose-escalation study”. The Lancet388 (10063): 3017. doi:10.1016/S0140-6736(16)31408-8.
Nusinersen
Nusinersen sodium colored.svg
Clinical data
Trade names Spinraza
Synonyms IONIS-SMNRx, ISIS-SMNRx
AHFS/Drugs.com Multum Consumer Information
License data
Routes of
administration
Injection into cerebrospinal fluid
ATC code
Legal status
Legal status
Pharmacokinetic data
Metabolism Exonuclease (3’- and 5’)-mediated hydrolysis
Biological half-life 135–177 days (in CSF), 63–87 days (in plasma)
Identifiers
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
Chemical and physical data
Formula C234H323N61Na17O128P17S17[2]
Molar mass 7501 Da[2]
3D model (JSmol)

////////////////Nusinersen sodium, Spinraza, ヌシネルセンナトリウム, FDA 2016, EU 2017, JAPAN 2017

CC1=CN(C(=O)NC1=O)C2C(C(C(O2)CO)OP(=S)(O)OCC3C(C(C(O3)N4C=C(C(=NC4=O)N)C)OCCOC)OP(=S)(O)OCC5C(C(C(O5)N6C=NC7=C6N=CN=C7N)OCCOC)OP(=S)(O)OCC8C(C(C(O8)N9C=C(C(=NC9=O)N)C)OCCOC)OP(=S)(O)OCC1C(C(C(O1)N1C=C(C(=O)NC1=O)C)OCCOC)OP(=S)(O)OCC1C(C(C(O1)N1C=C(C(=O)NC1=O)C)OCCOC)OP(=S)(O)OCC1C(C(C(O1)N1C=C(C(=O)NC1=O)C)OCCOC)OP(=S)(O)OCC1C(C(C(O1)N1C=C(C(=NC1=O)N)C)OCCOC)OP(=S)(O)OCC1C(C(C(O1)N1C=NC2=C1N=CN=C2N)OCCOC)OP(=S)(O)OCC1C(C(C(O1)N1C=C(C(=O)NC1=O)C)OCCOC)OP(=S)(O)OCC1C(C(C(O1)N1C=NC2=C1N=CN=C2N)OCCOC)OP(=S)(O)OCC1C(C(C(O1)N1C=NC2=C1N=CN=C2N)OCCOC)OP(=S)(O)OCC1C(C(C(O1)N1C=C(C(=O)NC1=O)C)OCCOC)OP(=S)(O)OCC1C(C(C(O1)N1C=NC2=C1N=C(NC2=O)N)OCCOC)OP(=S)(O)OCC1C(C(C(O1)N1C=C(C(=NC1=O)N)C)OCCOC)OP(=S)(O)OCC1C(C(C(O1)N1C=C(C(=O)NC1=O)C)OCCOC)OP(=O)(OCC1C(C(C(O1)N1C=NC2=C1N=C(NC2=O)N)OCCOC)OP(=S)(O)OCC1C(C(C(O1)N1C=NC2=C1N=C(NC2=O)N)OCCOC)O)S)OCCOC

ALOFISEL, darvadstrocel Cx-601


 

ALOFISEL

darvadstrocel

Cx-601

On 14 December 2017, the Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion, recommending the granting of a marketing authorisation for the medicinal product Alofisel, intended for the treatment of complex perianal fistulas in patients with Crohn’s disease. As Alofisel is an advanced therapy medicinal product, the CHMP positive opinion is based on an assessment by the Committee for Advanced Therapies. Alofisel was designated as an orphan medicinal product on 8 October 2009. The applicant for this medicinal product is Tigenix, S.A.U.

Alofisel will be available as a suspension for injection (5 million cells/ml). The active substance of Alofisel is darvadstrocel. Darvadstrocel contains expanded adipose stem cells which, once activated, impair proliferation of lymphocytes and reduce the release of pro-inflammatory cytokines at inflammation sites. This immunoregulatory activity reduces inflammation and may allow the tissues around the fistula tract to heal.

The benefits with Alofisel are its ability to improve the healing process of complex perianal fistulas in patients with Crohn’s disease. The most commonly reported side effects include anal abscess and fistula, as well as procedural pain and proctalgia.

The full indication is: “Alofisel is indicated for the treatment of complex perianal fistulas in adult patients with non-active/mildly active luminal Crohn’s disease, when fistulas have shown an inadequate response to at least one conventional or biologic therapy. Alofisel should be used after conditioning of fistula, see section 4.2.”

It is proposed that Alofisel be administered by specialist physicians experienced in the diagnosis and treatment of conditions for which Alofisel is indicated.

Detailed recommendations for the use of this product will be described in the summary of product characteristics (SmPC), which will be published in the European public assessment report (EPAR) and made available in all official European Union languages after the marketing authorisation has been granted by the European Commission.

Name Alofisel
INN or common name darvadstrocel
Therapeutic area Rectal Fistula
Active substance darvadstrocel
Date opinion adopted 14/12/2017
Company name Tigenix, S.A.U.
Status Positive
Application type Initial authorisation

New medicine to treat perianal fistulas in patients with Crohn’s disease

CHMP summary of positive opinion for Alofisel

Image result for ALOFISEL

Cx601

Cx601 is a local administration of expanded adipose-derived stem cells (eASCs) for the treatment of complex perianal fistulas in Crohn’s disease patients. The treatment is administered as a single dose and has been proven to have long-term efficacy in the healing of complex perianal fistulas in Crohn’s disease patients (ADMIRE-CD study completed in 2015 with positive 2 year follow-up data). The 24-week results of this trial were published in The Lancet in July 2016.

Cx601 has been designated as an orphan drug by the EMA and SwissMedic, in Switzerland.

On 4th July 2016, Takeda Pharmaceuticals acquired an exclusive right to develop and commercialize Cx601 for complex perianal fistulas in Crohn’s disease patients outside of the U.S. Takeda is a leading pharmaceutical company in the gastroenterology space. TiGenix retains full rights to the product in the US as well as to the development of Cx601 in other indications.

  • OriginatorCellerix
  • DeveloperLa Fundacion para la Investigacion Biomedica del Hospital Universitario La Paz; Takeda; TiGenix
  • ClassStem cell therapies
  • Mechanism of ActionCell replacements
  • Orphan Drug StatusYes – Rectal fistula
  • New Molecular EntityNo

Highest Development Phases

  • PreregistrationRectal fistula
  • No development reportedRectovaginal fistula

Most Recent Events

  • 15 Dec 2017Committee for Medicinal Products for Human Use (CHMP) and Committee for Advanced Therapies (CAT) recommend approval for darvadstrocel for Rectal fistula in European Union
  • 14 Dec 2017TiGenix in-licenses patents related to adipose-derived mesenchymal stem cells from Mesoblast
  • 16 Nov 2017Cx 601 is now called darvadstrocel

15/12/2017

New medicine to treat perianal fistulas in patients with Crohn’s disease

Alofisel is the tenth advanced therapy recommended for marketing authorisation

The European Medicines Agency (EMA) has recommended granting a marketing authorisation in the European Union (EU) for a new advanced therapy medicinal product (ATMP) for the treatment of complex perianal fistulas in patients with Crohn’s disease. Alofisel is the tenth ATMP that has received a positive opinion from the Agency’s Committee for Medicinal Products for Human Use (CHMP).

Crohn’s disease is a long-term condition that causes inflammation of the digestive system or gut. Apart from affecting the lining of the bowel, inflammation may also go deeper into the bowel wall. Perianal fistulas are common complications of Crohn’s disease and occur when an abnormal passageway develops between the rectum and the outside of the body. These can lead to incontinence (a lack of control over the opening of the bowels) and sepsis (blood infection). Complex fistulas are known to be more treatment resistant than simple fistulas. There is currently no cure for Crohn’s disease, so the aim of treatment is to stop the inflammatory process, relieve symptoms and avoid surgery wherever possible. Crohn’s disease can affect people of all ages, with a higher incidence in the younger population.

The active substance of Alofisel is darvadstrocel. Darvadstrocel contains expanded adipose stem cells which, once activated, impair proliferation of lymphocytes and reduce the release of pro-inflammatory cytokines at inflammation sites. This immunoregulatory activity reduces inflammation and may allow the tissues around the fistula tract to heal.

The benefits of Alofisel were studied in a main phase III clinical trial involving 212 patients. After 24 weeks of treatment, half of the patients treated with Alofisel (49.5%) were in remission, compared to a third of the patients under placebo. An extended ongoing follow-up study, which will cover a period of up to 104 weeks of treatment, has supported this result to date.

Although there is a moderate difference between the treatment groups, the effect is considered to be clinically meaningful when other treatment options for fistulas have failed. The most common side effects observed include anal abscess and fistula, as well as procedural pain and proctalgia.

Alofisel was assessed by the Committee for Advanced Therapies (CAT), EMA’s specialised scientific committee for ATMPs, such as gene or cell therapies. At its December 2017 meeting, the CAT recommended a positive opinion for Alofisel to the CHMP. The CHMP agreed with the CAT’s recommendation and adopted a positive opinion for the authorisation of Alofisel across the EU at its 11-14 December 2017 meeting.

Because complex perianal fistulas are rare, Alofisel was granted an orphan designation. As always at time of approval, this orphan designation will now be reviewed by EMA’s Committee for Orphan Medicinal Products (COMP) to determine whether the information available to date allows maintaining Alofisel’s orphan status and granting this medicine ten years of market exclusivity.

The opinion adopted by the CHMP is an intermediary step on Alofisel’s path to patient access. The CHMP opinion will now be sent to the European Commission for the adoption of a decision on an EU-wide marketing authorisation. Once a marketing authorisation has been granted, decisions about price and reimbursement will take place at the level of each Member State, taking into account the potential role/use of this medicine in the context of the national health system of that country.

Takeda and TiGenix announce that Cx601 (darvadstrocel) has received a positive CHMP opinion to treat complex perianal fistulas in Crohn’s disease

December 15, 2017 Osaka, Japan and Leuven, Belgium
  • First allogeneic stem cell therapy to receive positive CHMP opinion in Europe 
  • Cx601 offers potential new treatment option for patients who do not respond to current available therapies and are subject to numerous invasive surgeries1

Takeda Pharmaceutical Company Limited (TSE: 4502) (“Takeda”) and TiGenix NV (Euronext Brussels and NASDAQ: TIG) (“TiGenix”) today announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA), in conjunction with the Committee for Advanced Therapies (CAT), has adopted a positive opinion recommending a marketing authorization (MA) for investigational compound Cx601 (darvadstrocel). Cx601 is expected to be indicated for the treatment of complex perianal fistulas in adult patients with non-active/mildly active luminal Crohn’s disease, when fistulas have shown an inadequate response to at least one conventional or biologic therapy.2 This recommendation marks the first allogeneic stem cell therapy to receive a positive CHMP opinion in Europe.

 

“Following today’s news, physicians and surgeons in Europe can look forward to offering these Crohn’s disease patients a novel and minimally invasive alternative treatment option in the future, which in clinical trials achieved higher combined remission and lower relapse rates* than the current standard of care,” said Professor Julian Panés, Head of the Gastroenterology Department at the Hospital Clinic of Barcelona (Spain) and President of the European Crohn’s and Colitis Organisation (ECCO). “Perianal fistulas are estimated to affect up to 28% of patients in the first two decades after Crohn’s disease diagnosis and Cx601 offers new hope for those suffering from this severe and debilitating condition.”

Cx601 was assessed by the CAT, the EMA’s specialized scientific committee for Advanced Therapy Medicinal Products (ATMP), such as gene or cell therapies. The positive CHMP opinion was based on results from TiGenix’s Phase III ADMIRE-CD pivotal trial. The ADMIRE-CD trial is a randomized, double-blind, controlled, Phase III trial designed to investigate the efficacy and safety of investigational compound Cx601.3 24-week results were published in The Lancet and showed that Cx601 achieved statistically significant superiority versus the control group in the primary efficacy endpoint of combined remission.**,1 In addition, the rates and types of treatment related adverse events (non-serious and serious) and number of discontinuations due to adverse events were comparable between Cx601 and control arms, the most common of which were anal abscess and proctalgia.1Further follow-up data indicated that Cx601 maintained long-term remission of treatment refractory complex perianal fistulas in patients with Crohn’s disease over 52 weeks.4

Dr. María Pascual, VP Regulatory Affairs and Corporate Quality at TiGenix, said, “We believe that this first approval recommendation for an allogeneic stem cell therapy in Europe reflects the maturity of our technology and its potential to offer new approaches for difficult to treat conditions. We have worked closely with the EMA and provided a robust data package from a well-designed clinical trial with challenging endpoints. In parallel, we will continue working hard to obtain regulatory approval in the U.S. and to develop Cx601 for additional indications, to fulfil our aim of allowing patients to benefit from the full potential of Cx601 across multiple geographies and diseases.”

The opinion will now be referred to the European Commission with a decision anticipated in the coming months. An MA will allow Cx601 to be marketed in all 28 member states of the EU, plus Norway, Iceland and Lichtenstein.

 

Cx601 has been licensed to Takeda for the exclusive development and commercialization outside of the U.S. Receipt of the MA will trigger a milestone payment from Takeda to TiGenix of €15 million. The companies have been working closely together to advance preparations for commercialization, with a potential start of the commercial launch by Takeda anticipated after MA is transferred from TiGenix to Takeda.

 

“Today’s positive CHMP opinion is a crucial step to bringing a new treatment option to patients with complex perianal fistulas in Crohn’s disease,” said Dr. Asit Parikh, Head of Takeda’s Gastroenterology Therapeutic Area Unit. “We would like to thank the scientific community and patients involved in the ADMIRE-CD trial for their support in helping us reach this important milestone. We remain committed to delivering innovative, therapeutic options for patients suffering from gastrointestinal disorders.”

Complex perianal fistulas are considered one of the most disabling complications of Crohn’s disease5 and can cause intense pain6 and swelling, infection and incontinence.1 Despite available therapies and surgical advancements, they currently remain challenging for clinicians to treat7 and have a significant negative impact on patient quality of life.6

 


* Relapse defined as reopening of any of the treated external openings with active drainage as clinically assessed, or development of perianal collection ≥2cm of the treated perianal fistula confirmed by centrally blinded pelvic MRI assessment in patients with clinical remission at any previous visit

** Combined remission defined as clinical assessment of closure of all treated external openings draining at baseline, despite gentle finger compression, and absence of collections >2cm confirmed by pelvic MRI

About TiGenix

TiGenix NV (Euronext Brussels and NASDAQ: TIG) is an advanced biopharmaceutical company developing novel therapies for serious medical conditions by exploiting the anti-inflammatory properties of allogeneic, or donor-derived, stem cells.

 

TiGenix´ lead product, Cx601, has successfully completed a European Phase III clinical trial for the treatment of complex perianal fistulas – a severe, debilitating complication of Crohn’s disease. Cx601 has been filed for regulatory approval in Europe and a global Phase III trial intended to support a future U.S. Biologic License Application (BLA) started in 2017. TiGenix has entered into a licensing agreement with Takeda, a global pharmaceutical company active in gastroenterology, under which Takeda acquired the exclusive right to develop and commercialize Cx601 for complex perianal fistulas outside the U.S. TiGenix’ second adipose-derived product, Cx611, is undergoing a Phase I/II trial in severe sepsis – a major cause of mortality in the developed world. Finally, AlloCSC-01, targeting acute ischemic heart disease, has demonstrated positive results in a Phase I/II trial in acute myocardial infarction (AMI). TiGenix is headquartered in Leuven (Belgium) and has operations in Madrid (Spain) and Cambridge, MA (USA). For more information, please visit http://www.tigenix.com.

 

About Cx601

Cx601 is a local administration of allogeneic (or donor derived) expanded adipose-derived stem cells (eASCs) for the treatment of complex perianal fistulas in adult Crohn’s disease patients that have previously shown an inadequate response to at least one conventional therapy or biologic therapy. Crohn’s disease is a chronic inflammatory disease of the intestine and complex perianal fistulas are a severe and debilitating complication for which there is currently no effective treatment. Cx601 was granted orphan drug designation by the European Commission in 2009 and by the U.S Food and Drug Administration (FDA) in 2017. TiGenix completed a European Phase III clinical trial (ADMIRE-CD) in August 2015 in which both the primary endpoint and the safety and efficacy profile were met, with patients receiving Cx601 showing a 44% greater probability of achieving combined remission compared to control (placebo).1 A follow-up analysis was completed at 52 weeks4 and 104 weeks post-treatment, confirming the sustained efficacy and safety profile of the product. The 24-week results of the Phase III ADMIRE-CD trial were published in The Lancet  in July 2016.1 Based on the positive 24 weeks Phase III study results, TiGenix submitted a Marketing Authorization Application to the European Medicines Agency (EMA). A global Phase III clinical trial (ADMIRE-CD II) intended to support a future U.S. Biologic License Application (BLA) started in 2017, based on a trial protocol that has been agreed with the FDA through a special protocol assessment procedure (SPA) (clinicaltrials.gov; NCT03279081). ADMIRE-CD II is a randomized, double-blind, placebo-controlled study designed to confirm the efficacy and safety of a single administration of Cx601 for the treatment of complex perianal fistulas in Crohn’s disease patients. In July 2016, TiGenix entered into a licensing agreement with Takeda, a global pharmaceutical company active in gastroenterology, under which Takeda acquired exclusive rights to develop and commercialize Cx601 for complex perianal fistulas in Crohn’s patients outside of the U.S.

 

Forward-looking information

This press release may contain forward-looking statements and estimates with respect to the anticipated future performance of TiGenix and the market in which it operates. Certain of these statements, forecasts and estimates can be recognised by the use of words such as, without limitation, “believes”, “anticipates”, “expects”, “intends”, “plans”, “seeks”, “estimates”, “may”, “will” and “continue” and similar expressions. They include all matters that are not historical facts. Such statements, forecasts and estimates are based on various assumptions and assessments of known and unknown risks, uncertainties and other factors, which were deemed reasonable when made but may or may not prove to be correct. Actual events are difficult to predict and may depend upon factors that are beyond the Company’s control. Therefore, actual results, the financial condition, performance or achievements of TiGenix, or industry results, may turn out to be materially different from any future results, performance or achievements expressed or implied by such statements, forecasts and estimates. Given these uncertainties, no representations are made as to the accuracy or fairness of such forward-looking statements, forecasts and estimates. Furthermore, forward-looking statements, forecasts and estimates only speak as of the date of the publication of this press release. TiGenix disclaims any obligation to update any such forward-looking statement, forecast or estimates to reflect any change in the Company’s expectations with regard thereto, or any change in events, conditions or circumstances on which any such statement, forecast or estimate is based, except to the extent required by Belgian law.

 

References

1 Panés J, García-Olmo D, Van Assche G, et al., Expanded allogeneic adipose-derived mesenchymal stem cells (Cx601) for complex perianal fistulas in Crohn’s disease: a phase 3 randomized, double-blind controlled trial. The Lancet. 2016; 388(10051): 1281-1290.

2 European Medicines Agency. Available at: http://www.ema.europa.eu/ema/. Accessed December 15, 2017.

3 Clinicaltrials.gov. Adipose Derived Mesenchymal Stem Cells for Induction of Remission in Perianal Fistulizing Crohn’s Disease (ADMIRE-CD). Available at: https://clinicaltrials.gov/ct2/show/NCT01541579?term=cx601 &rank=2. Published February 2012. Accessed December 15, 2017.

4 Panés J, García-Olmo D, Van Assche G, et al., Long-term efficacy and safety of Cx601, allogeneic expanded adipose-derived mesenchymal stem cells, for complex perianal fistulas in Crohn’s Disease: 52-week results of a phase III randomized controlled trial. ECCO 2017; Barcelona: Abstract OP009.

5 Marzo M, Felice C, Pugliese D, et al., Management of perianal fistulas in Crohn’s disease: An up-to-date review. World J Gastroenterol. 2015; 21(5): 1394-1395.

6 Mahadev S, Young JM, Selby W, et al., Quality of life in perianal Crohn’s disease: what do patients consider important? Dis Colon Rectum. 2011; 54(5): 579-585.

7 Geltzeiler C, Wieghard N and Tsikitis V. Recent developments in the surgical management of perianal fistula for Crohn’s disease. Ann Gastroenterol. 2014; 27(4): 320-330.

Notes

  • The applicant for Alofisel is Tigenix, S.A.U.
  1. AGA technical review on perianal Crohn’s disease 2003; 125(5):1508-1530
  2. TiGenix company presentation, June 2017 (http://tigenix.com/wp-content/themes/tigenix/images/TiGenix_Corporate_Presentation.pdf , accessed on June 22nd, 2017).
  3. Panes J et al. Long-term efficacy and safety of Cx601, allogeneic expanded adipose-derived mesenchymal stem cells, for complex perianal fistulas in Crohn’s disease: 52-week results of a Phase III randomized controlled trial. The 12th Congress of ECCO, February 15-18, 2017, Barcelona, Spain
  4. Cohen RD et al, 2008. Effects of fistula on healthcare costs and utilization for patients with Crohn’s disease treated in a managed care environment.
  5. nice.org.uk
  6. Gene therapy: understanding the science, assessing the evidence, and paying for the value: a report from the 2016 ICER membership policy summit. March 2017.
  7. Chaparro M. et al., 2013 Health care costs of complex perianal fistula in Crohn’s disease.
  8. Takeda’s press release, January 5, 2018.
  9. http://tigenix.com/wp-content/themes/tigenix/images/TiGenix_Corporate_Presentation.pdf

/////////////////ALOFISEL, darvadstrocel, Cx-601, eu 2017, ema 2017

PADELIPORFIN


Padeliporfin.png

2D chemical structure of 759457-82-4

PADELIPORFIN

759457-82-4; 457P824,

RN: 759457-82-4
UNII: EEO29FZT86

3-[(2S,3S,12R,13R)-8-acetyl-13-ethyl-20-(2-methoxy-2-oxoethyl)-3,7,12,17-tetramethyl-18-(2-sulfoethylcarbamoyl)-2,3,12,13-tetrahydroporphyrin-22,24-diid-2-yl]propanoic acid;palladium(2+)

 (SP-4-2)-[(7S,8S,17R,18R)-13-acetyl-18-ethyl-5-(2-methoxy-2-oxoethyl)-2,8,12,17-tetramethyl-3-[[(2-sulfoethyl)amino]carbonyl]-21H,23H-porphine-7-propanoato (4-)-kN21,kN22,kN23,kN24] palladate(2-)

Palladate(2-​)​, [(7S,​8S,​17R,​18R)​-​13-​acetyl-​18-​ethyl-​7,​8-​dihydro-​5-​(2-​methoxy-​2-​oxoethyl)​-​2,​8,​12,​17-​tetramethyl-​3-​[[(2-​sulfoethyl)​amino]​carbonyl]​-​21H,​23H-​porphine-​7-​propanoato(4-​)​-​κN21,​κN22,​κN23,​κN24]​-​, (SP-​4-​2)​-
Coordination Compound

Other Names

  • (SP-4-2)-[(7S,8S,17R,18R)-13-Acetyl-18-ethyl-7,8-dihydro-5-(2-methoxy-2-oxoethyl)-2,8,12,17-tetramethyl-3-[[(2-sulfoethyl)amino]carbonyl]-21H,23H-porphine-7-propanoato(4-)-κN21,κN22,κN23,κN24]palladate(2-)
Molecular Formula: C37H43N5O9PdS
Molecular Weight: 840.257 g/mol

img

Chemical Formula: C37H41K2N5O9PdS
Molecular Weight: 916.43

cas 698393-30-5

WST11; WST-11; WST 11; Stakel; padeliporfin; palladiumbacteriopheophorbide monolysine taurine.

Palladate(2-​)​, [(7S,​8S,​17R,​18R)​-​13-​acetyl-​18-​ethyl-​7,​8-​dihydro-​5-​(2-​methoxy-​2-​oxoethyl)​-​2,​8,​12,​17-​tetramethyl-​3-​[[(2-​sulfoethyl)​amino]​carbonyl]​-​21H,​23H-​porphine-​7-​propanoato(4-​)​-​κN21,​κN22,​κN23,​κN24]​-​, potassium (1:2)​, (SP-​4-​2)​-

Tookad : EPAR -Product Information

Tookad : EPAR – Summary for the public (English only) 29/11/2017

Product details

Pharmacotherapeutic group

Antineoplastic agents

Therapeutic indication

Tookad is indicated as monotherapy for adult patients with previously untreated, unilateral, low risk, adenocarcinoma of the prostate with a life expectancy ≥ 10 years and:

  • Clinical stage T1c or T2a;
  • Gleason Score ≤ 6, based on high-resolution biopsy strategies;
  • PSA ≤ 10 ng/mL;
  • 3 positive cancer cores with a maximum cancer core length of 5 mm in any one core or 1-2 positive cancer cores with ≥ 50 % cancer involvement in any one core or a PSA density ≥ 0.15 ng/mL/cm³.
Name Tookad
Agency product number EMEA/H/C/004182
Active substance padeliporfin di-potassium
International non-proprietary name(INN) or common name padeliporfin
Therapeutic area Prostatic Neoplasms
Anatomical therapeutic chemical (ATC) code L01XD07
Additional monitoring This medicine is under additional monitoring. This means that it is being monitored even more intensively than other medicines. For more information, see medicines under additional monitoring.
Marketing-authorisation holder STEBA Biotech S.A
Revision 0
Date of issue of marketing authorisation valid throughout the European Union 10/11/2017

Contact address:

STEBA Biotech S.A
7 place du theatre
L-2613 Luxembourg
Luxembourg

Padeliporfin is a vascular-acting photosensitizer consisting of a water-soluble, palladium-substituted bacteriochlorophyll derivative with potential antineoplastic activity. Upon administration, paldeliporfin is activated locally when the tumor bed is exposed to low-power laser light; reactive oxygen species (ROS) are formed upon activation and ROS-mediated necrosis may occur at the site of interaction between the photosensitizer, light and oxygen. Vascular-targeted photodynamic therapy (VTP) with padeliporfin may allow tumor-site specific cytotoxicity while sparing adjacent normal tissues.

WST-11 (Stakel) is a water-soluble bacteriochlorophyll (chemical structure shown below) derivative coordinated with palldium, which has maximum absorption wavelength in the near infrared (753 nm) and rapid clearance from the body ( t 1/2 = 0.37 hour for a 10-mg/kg drug dose in the rat and t 1/2 = 0.51 hour, 1 hour, and 2.65 hours for 1.25-, 2.5-, and 5-mg/kg drug doses, respectively. It binds to serum albumin and has potent antivascular activity through the generation of hydroxyl radicals when stimulated by the proper light wavelength.

Image result for PADELIPORFIN

Photodynamic therapy (PDT) is a non-surgical treatment of tumors in which non-toxic drugs and non-hazardous photosensitizing irradiation are combined to generate cytotoxic reactive oxygen species in situ. This technique is more selective than the commonly used tumor chemotherapy and radiotherapy. To date, porphyrins have been employed as the primary photosensitizing agents in clinics. However, current sensitizers suffer from several deficiencies that limit their application, including mainly: (1) relatively weak absorption in the visible spectral range which limits the treatment to shallow tumors; (2) accumulation and long retention of the sensitizer in the patient skin, leading to prolonged (days to months) skin phototoxicity; and (3) small or even no differentiation between the PDT effect on illuminated tumor and non-tumor tissues. The drawbacks of current drugs inspired an extensive search for long wavelength absorbing second-generation sensitizers that exhibit better differentiation between their retention in tumor cells and skin or other normal tissues.

In order to optimize the performance of the porphyrin drugs in therapeutics and diagnostics, several porphyrin derivatives have been proposed in which, for example, there is a central metal atom (other than Mg) complexed to the four pyrrole rings, and/or the peripheral substituents of the pyrrole rings are modified and/or the macrocycle is dihydrogenated to chlorophyll derivatives (chlorins) or tetrahydrogenated to bacteriochlorophyll derivatives (bacteriochlorins).

Due to their intense absorption in favorable spectral regions (650-850 nm) and their ready degradation after treatment, chlorophyll and bacteriochlorophyll derivatives have been identified as excellent sensitizers for PDT of tumors and to have superior properties in comparison to porphyrins, but they are less readily available and more difficult to handle.

Bacteriochlorophylls are of potential advantage compared to the chlorophylls because they show intense near-infrared bands, i.e. at considerably longer wavelengths than chlorophyll derivatives.

The spectra, photophysics, and photochemistry of native bacteriochlorophylls (Bchls) have made them optimal light-harvesting molecules with clear advantages over other sensitizers presently used in PDT. In particular, these molecules have a very high extinction coefficient at long wavelengths (λmax=760-780 nm, ε=(4-10)xl04 M-1cm-1), where light penetrates deeply into tissues. They also generate reactive oxygen species (ROS) at a high quantum yield (depending on the central metal).

Under normal delivery conditions, i.e. in the presence of oxygen at room temperature and under normal light conditions, the BChl moieties are labile and have somewhat lower quantum yields for triplet state formation, when compared with, e.g., hematoporphyrin derivative (HPD). However, their possible initiation of biological redox reactions, favorable spectral characteristics and their ready degradation in vivo result in the potential superiority of bacteriochlorophylls over other compounds, e.g. porphyrins and chlorophylls, for PDT therapy and diagnostics and for killing of cells, viruses and bacteria in samples and in living tissue. Chemical modification of bacteriochlorophylls is expected to further improve their properties, but this has been very limited due to lack of suitable methods for the preparation of such modified bacteriochlorophylls .

The biological uptake and PDT efficacy of metal-free derivatives of Bchl have been studied with the objective to manipulate the affinity of the sensitizers to the tumor cellular compartment. Cardinal to this approach is the use of highly lipophilic drugs that may increase the accumulation of the drug in the tumor cells, but also renders its delivery difficult. In addition, the reported biodistribution shows significant phototoxic drug levels in non-tumor tissues over prolonged periods (at least days) after administering the drug.

In applicant’s previous Israel Patent No. 102645 and corresponding EP 0584552, US 5,726,169, US 5,726,169, US 5,955,585 and US 6,147,195, a different approach was taken by the inventors. Highly efficient anti- vascular sensitizers that do not extravasate from the circulation after administration and have short lifetime in the blood were studied. It was expected that the inherent difference between vessels of normal and abnormal tissues such as tumors or other tissues that rely on neovessels, would enable relatively selective destruction of the abnormal tissue. Hence, it was aimed to synthesize Bchl derivatives that are more polar and, hence, have better chance to stay in the vascular compartment, where they convey the primary photodynamic effect. To this end, the geranylgeranyl residue at the C-17 position of Bchl a (Compound 1, depicted in Scheme 1 herein) has been replaced by various residues such as amino acids, peptides, or proteins, which enhance the sensitizer hydrophilicity. One particular derivative, Bchl-Ser (Scheme 1, Compound 1, wherein R is seryl), was found to be water-soluble and highly phototoxic in cell cultures. Following infraperitoneal injection, the Bchl-Ser cleared from the mouse blood and tissues bi-exponentially in a relatively short time (t1/2~2 and 16 h, respectively). Clearance from the circulation was even faster following intravenous injection. Under the selected treatment protocol (light application within minutes after drug injection), phototoxicity was predominantly conferred to the tumor vasculature (Rosenbach-

Belkin et al., 1996; Zilberstein et al., 2001 and 1997). However, unfortunately, like native Bchl, the Bchl-Ser derivative undergoes rapid photo-oxidation, forming the corresponding 2-desvinyl-2-acetyl-chlorophyllide ester and other products.

To increase the stability of the Bchl derivatives, the central Mg atom was replaced by Pd in the later applicant’s PCT Publication WO 00/33833 and US 6,569,846. This heavy atom was previously shown to markedly increase the oxidation potential of the Bchl macrocycle and, at the same time, to greatly enhance the intersystem-crossing (ISC) rate of the molecule to its triplet state. The metal replacement was performed by direct incorporation of Pd2+ ion into a Bpheid molecule, as described in WO 00/33833. Based on the pigment biodistribution and pharmacokinetics, it was assumed that the derivative Pd-Bpheid remained in the circulation for a very short time with practically no extravasation to other tissues, and is therefore a good candidate for vascular-targeting PDT that avoids skin phototoxicity. The treatment effect on the blood vessels was demonstrated by intravital microscopy of treated blood vessels and staining with Evans-Blue. Using a treatment protocol with a minimal drug-to-light interval, Pd-Bpheid (also designated Tookad) was found to be effective in the eradication of different tumors in mice, rats and other animal models and is presently entering Phase I/II clinical trials in patients with prostate cancer that failed radiation therapy (Chen et al, 2002; Schreiber et al., 2002; Koudinova et al., 2003).

Because of its low solubility in aqueous solutions, the clinical use of Pd-Bpheid requires the use of solubilizing agents such as Cremophor that may cause side effects at high doses. It would be highly desirable to render the Pd-Bpheid water-soluble while retaining its physico-chemical properties. Alternatively, it would be desirable to prepare Bchl derivatives that are cytophototoxic and, at the same time, more water-soluble than Pd-Bpheid itself. Such water solubility is expected to further enhance the drug retention in the circulation and, thereby, the aforementioned selectivity. In addition, having no need to use carriers such as detergents or lyposomes, may prevent side effects.

SYNTHESIS

START FROM CAS 17499-98-8, Phorbine, magnesium deriv., Bacteriochlorophyll aP

STR1

PADELIPORFIN

Paper

Novel water-soluble bacteriochlorophyll derivatives for vascular-targeted photodynamic therapy: Synthesis, solubility, phototoxicity and the effect of serum proteins
Photochemistry and Photobiology (2005), 81, (July/Aug.), 983-993

PAPER

Journal of Medicinal Chemistry (2014), 57(1), 223-237

Abstract Image

With the knowledge that the dominant photodynamic therapy (PDT) mechanism of 1a (WST09) switched from type 2 to type 1 for 1b (WST11) upon taurine-driven E-ring opening, we hypothesized that taurine-driven E-ring opening of bacteriochlorophyll derivatives and net-charge variations would modulate reactive oxygen species (ROS) photogeneration. Eight bacteriochlorophyll a derivatives were synthesized with varying charges that either contained the E ring (2a5a) or were synthesized by taurine-driven E-ring opening (2b5b). Time-dependent density functional theory (TDDFT) modeling showed that all derivatives would be type 2 PDT-active, and ROS-activated fluorescent probes were used to investigate the photogeneration of a combination of type 1 and type 2 PDT ROS in organic- and aqueous-based solutions. These investigations validated our predictive modeling calculations and showed that taurine-driven E-ring opening and increasing negative charge generally enhanced ROS photogeneration in aqueous solutions. We propose that these structure–activity relationships may provide simple strategies for designing bacteriochlorins that efficiently generate ROS upon photoirradiation.

Modulation of Reactive Oxygen Species Photogeneration of Bacteriopheophorbide a Derivatives by Exocyclic E-Ring Opening and Charge Modifications

 Department of Pharmaceutical Sciences, Leslie L. Dan Faculty of Pharmacy, University of Toronto, 144 College Street, Toronto, Ontario M5S 3M2, Canada
 Ontario Cancer Institute and Techna Institute, UHN, 101 College Street, Toronto, Ontario M5G 1L7, Canada
§ Department of Chemical Engineering and Applied Chemistry, University of Toronto, 200 College Street, Toronto, Ontario M5S 3E5, Canada
J. Med. Chem.201457 (1), pp 223–237
DOI: 10.1021/jm401538h
*Tel: 416-581-7666. Fax 416-581-7667. E-mail: gzheng@uhnresearch.ca.
Palladium 31-Oxo-15-methoxycarbonylmethyl-rhodobacteriochlorin 13′-(2-Sulfethyl)amide (1b)
……………… The dried crude product was dissolved in 200 μL of DMSO and purified by reverse-phase HPLC. The product was quantified spectrophotometrically, the identity was characterized using ESI+MS and UV–vis spectroscopy, and the purity was found to be >95% using HPLC–MS. This yielded 0.21 mg (250 nmol) of 1b(0.7% yield). ESI+MS: [M]+ = 840 m/z. UV–vis (MeOH, λmax): 748, 517, 385, 332 nm.
PATENT

CHEMICAL EXAMPLES

Example 1. Palladium 31-oxo-15-methoxycarbonylmethyl-Rhodobacteriochlorin 131-(2-sulfoethyl)amide dipotassium salt ( Compound 4)

Nine hundred and thirty five (935) mg of Pd-Bpheid (3) were dissolved in a 1 L round bottom flask with 120 ml of DMSO while stirring under Argon (bubbled in the solution). Taurine (1288 mg) was dissolved in 40 ml of 1M K2HPO4 buffer, and the pH of the solution was adjusted to 8.2 (with HCl ). This aqueous solution was added into the DMSO solution while stirring, and the Argon was bubbled in the solution for another 20 minutes. Then the reaction mixture was evaporated at 30°C for 3.5 hours under ~2 mbar and then for another 2 hours at 37°C to a complete dryness. The dry solids were dissolved in 300 ml of MeOH and the colored solution was filtered through cotton wool to get rid of buffer salts and taurine excess.

The progress of the reaction was determined by TLC (Rf of unreacted Pd- Bpheid is 0.8-0.85 and of the reaction (aminolysis) product is 0.08-0.1) and by following the optical absorption spectrum of the reaction mixture after liophylization and resolubihzation in MeOH. The absorption spectrum was characterized by a Qytransition shift from 756 nm (for Pd-Bpheid) to 747 nm (for the product 4) and by Qx shift from 534 nm of Pd-Bpheid to 519 nm (of the product 4). The MeOH was evaporated and the product 4 was purified by HPLC with ODS-A 250X20 S10P μm column (YMC, Japan). Solvent A: 95% 0.005 M phosphate buffer, pH 8.0 and 5% MeOH. Solvent B: 100% MeOH. The dry solid was dissolved in 42 ml of distilled water and injected in portions of 1.5 ml each .

The elution profile is described in Table 1. The product 4_(Scheme 1, see below) was eluted and collected at ~ 9-11 minutes. The main impurities, collected after at 4-7 min (ca 5-10%), corresponded to byproduct(s) with the proposed structure 7. Peaks at 22-25 min (ca 2-5%) possibly corresponded to the iso-form of the main product 4 and untreated Pd-Bpheid residues.

The solvent (aqueous methanol) was evaporated under reduced pressure. Then, the purified product 4 ]was re-dissolved in ~150 ml MeOH and filtered through cotton wool. The solvent was evaporated again and the solid pigment 4 was stored under Ar in the dark at -20°C. The reaction yield: ~90% (by weight, relative to 3).

The structure of product 4 was confirmed by electrospray mass spectroscopy. (ESI-MS, negative mode, Fig.2), (peaks at 875 (M–K-H), 859 (M–2K-H+Na), 837 (M–2K), 805 (M2K-H-OMe), 719) and 1H-NMR spectrum (Fig. 4 in MeOH-d4). Table 4 provides the shifts (in ppm units) of the major NMR peaks.

Optical absorption (UN-VIS) spectrum (MeOH): λ, 747 (1.00), 516 (0.13), 384 (0.41), 330 (0.50); ε747 (MeOH) is 1.2 x 105 mol-1 cm _1.

ΝMR (MeOH-d4): 9.38 (5-H, s), 8.78 (10-H, s), 8.59 (20-H, s), 5.31 and 4.95 (151-CH2, dd), 4.2-4.4 (7,8,17,18-H, m), 3.88 (153-Me, s), 3.52 (21-Me, s), 3.19 (121 -Me, s), 3.09 (32-Me, s), 1.92-2.41, 1.60-1.75 (171, 172-CH2, m), 2.19 (81-CH2, m), 1.93 (71-Me, d), 1.61 (181-Me, d), 1.09 (82-Me, t), 3.62, 3.05 (CH2‘s of taurine).

Octanol/water partition ratio is 40:60.

Example 2. Preparation of 31-oxo-15-methoxycarbonylmethyl- Rhodobacteriochlorin 131-(2-sulfoethyl)amide dipotassium salt (Compound 5) One hundred and sixty (160) mg of taurine were dissolved in 5 ml of 1M

K2HPO4 buffer, and the pH of the solution was adjusted to 8.2. This solution was added to 120 mg of compound 2 dissolved in 15 ml of DMSO, and the reaction and following purification were analogous to those described in previous Example.

Absorption spectrum (MeOH): λ, 750 (1.00), 519 (0.30), 354 (1.18) nm.

ESI-MS (-): 734 (M–2K).

ΝMR (MeOH-d4): 9.31 (5-H, s), 8.88 (10-H, s), 8.69 (20-H, s), 5.45 and 5.25 (151-CH2, dd), 4.35 (7,18-H, m), 4.06 (8,17-H, m), 4.20 and 3.61 (2-CH2, m of taurine), 3.83 (153-Me, s), 3.63 (21-Me, s), 3.52 (3-CH2, m oftaurine), 3.33 (121-Me, s), 3.23 (32-Me, s), 2.47 and 2.16 (171-CH2, m), 2.32 and 2.16 (81-CH2, m), 2.12 and 1.65 (172-CH2, m), 1.91 (71-Me, d), 1.66 (181– Me, d), 1.07 (82-Me, t).

Octanol/water partition ratio is 60:40.

Example 3. Preparation of copper(II) 31-oxo-15-methoxycarbonylmethyl- Rhodobacteriochlorin 131-(2-sulfoethyl)amide dipotassium salt (Compound 10)

Fifty (50) mg of compound 5 of Example 2 and 35 mg of copper (II) acetate were dissolved in 40 ml of methanol, and argon was bubbled into solution for 10 minutes. Then 500 mg of palmitoyl ascorbate was added, and the solution was stirred for 30 min. The absorption spectrum was characterized by a Qy transition shift from 750 nm (for 5) to 768 nm (for the product 10) and by Qx shift from 519 nm of 5 to 537 nm (of the product 10). Then the reaction mixture was evaporated, re-dissolved in acetone and filtered through cotton wool to get rid of acetate salt excess. The acetone was evaporated and the product was additionally purified by HPLC at the conditions mentioned above with the elution profile, described in Table 2.

The solvent (aqueous methanol) was evaporated under reduced pressure. Then, the purified pigment 10 was re-dissolved in methanol and filtered through cotton wool. The solvent was evaporated again and the solid pigment 10 was stored under Ar in the dark at -20°C. Reaction yield: -90%.

Absorption spectrum (MeOH): λ, 768 (1.00), 537 (0.22), 387 (0.71) and 342 (0.79) nm.

ESI-MS (-): 795 (M–2K).

Octanol/water partition ratio is 40:60.

Example 4. Preparation of zinc 31-oxo-15-methoxycarbonylmethyl-Rhodobacteriochlorin 131-(2-sulfoethyl)amide dipotassium salt (Compound 11)

Zn insertion into compound 5 was carried out with Zn acetate in acetic acid as previously described (US Patent No. 5,726,169). Final purification was carried out by HPLC in the same conditions as for compound 5 in Example 2 above.

Absorption spectrum (MeOH): λ, 762 (1.00), 558 (0.26), 390 (0.62) and 355 (0.84) nm.

Octanol/water partition ratio is 50:50.

Example 5. Preparation of manganese(III) 31-oxo-15-methoxycarbonylmethyl-Rhodobacteriochlorin 131-(2-sulfoethyl)amide dipotassium salt (Compound 12)

Mn insertion into compound 5 was carried out with Zn acetate in acetic acid as previously described (WO 97/19081; US 6,333,319) with some modifications. Thus, fifty (50) mg of compound 5 in 10 ml of DMF were stirred with 220 mg of cadmium acetate and heated under argon atmosphere at 110°C about 15 min (Cd-complex formation is monitored by shifting Qx transition absorption band from 519 to 585 nm in acetone). Then the reaction mixture was cooled and evaporated. The dry residue was re-dissolved in 15 ml of acetone and stirred with manganese (II) chloride to form the Mn(III)-product 12. The product formation is monitored by shifting Qx transition band from 585 to 600 nm and Qy transition band from 768 to 828 nm in acetone. The acetone was evaporated and the product 12 was additionally purified by HPLC in the conditions mentioned in Example 2 above with the elution profile described in Table 3 below where the] solvent system consists of: A – 5% aqueous methanol, B -methanol.

The solvent (aqueous methanol) was evaporated under reduced pressure and the solid pigment 12 was stored under Ar in the dark at -20°C.

Absorption spectrum (MeOH): λ, 828 (1.00), 588 (0.32) and 372 (0.80) nm. Octanol/water partition ratio is 5:95.

Example 6. Preparation of palladium bacteriopheophorbide a 17 -(3-sulfo-1-oxy- succinimide)ester sodium salt (Compound 6)

Fifty (50) mg of Pd-Bpheid (compound 2), 80 mg of N-hydroxy- sulfosuccinimide (sulfoNHS) and 65 mg of 1-(3-dimethylaminopropyl)-3- ethylcarbodiimide (EDC) were mixed in 7 ml of dry DMSO for overnight at room temperature. Then the solvent was evacuated under reduced pressure. The dry residue was re-dissolved in chloroform (ca. 50 ml), filtered from insoluble material, and evaporated. The conversion was ab. 95%) (TLC). The product 6 was used later on without further chromatographic purification. ESI-MS (-): 890 (M–Na).

NMR (CDCl3): 9.19 (5-H, s), 8.49 (10-H, s), 8.46 (20-H, s), 5.82 (132-H, s), 4.04- 4.38 (7,8,17,18-H, m), 3.85 (134-Me, s), 3.47 (21-Me, s), 3.37 (^-Me, s), 3.09 (32– Me, s), 1.77 (71-Me, d), 1.70 (lδ’-Me, d), 1.10 (82-Me, t), 4.05 (CH2 of sNHS), 3.45 (CH ofs NHS).

Example 7. Preparation of palladium bacteriopheophorbide a 173-(3-sulfopropyl) amide potassium salt (Compound 7)

Ten (10) mg of compound 6 in 1 ml of DMSO was mixed with 20 mg of homotaurine (3-amino-1-propane-sulfonic acid) in 1 ml of 0.1 M K-phosphate buffer, pH 8.0 for overnight. Then the reaction mixture was partitioned in chloroform/water. The organic layer was dried over anhydrous sodium sulfate and evaporated. The dry residue was re-dissolved in chloroform-methanol (19:1) and applied to a chromatographic column with silica. The product 7 was obtained with chloroform-methanol (4:1) elution. The yield was about 80-90%.

ESI-MS (-): 834 (M-K) m/z.

NMR (MeOH-d4): 9.16 (5-H, s), 8.71 (10-H, s), 8.60 (20-H, s), 6.05 (132-H, s), 4.51, 4.39, 4.11, 3.98 (7,8,17,18-H, all m), 3.92 (134-Me, s), 3.48 (21-Me, s), 3.36 (121-Me, s), 3.09 (32-Me, s), 2.02-2.42 (171 arid 172-CH2, m), 2.15 ( 81-CH2, q), 1.81 (71-Me, d), 1.72 (181-Me, d), 1.05 (82-Me, t), 3.04, 2.68, and 2.32 (CH2‘s of homotaurine, m).

Example 8. Preparation of palladium 31-oxo-15-methoxycarbonylmethyl-Rhodo-bacteriochlorin 13 ,17 -di(3-sulfopropyl)amide dipotassium salt (Compound 8)

Ten (10) mg of compound 6 or 7 were dissolved in 3 ml of DMSO, mixed with 100 mg of homotaurine in 1 ml of 0.5 M K-phosphate buffer, pH 8.2, and incubated overnight at room temperature. The solvent was then evacuated under reduced pressure as described above, and the product 8 was purified on HPLC. Yield: 83%.

Absorption spectrum (MeOH): 747 (1.00), 516 (0.13), 384 (0.41), 330 (0.50), ε747 =1.3×105 modern-1.

ESI-MS(-):1011 (M–K), 994 (M–2K+Na),972 (M–2K), 775 (M–2K-CO2Me-homotaurineNHCH2CH2CH2SO3), 486 ([M-2K]/2)

NMR (MeOH-d4): 9.35 (5-H, s), 8.75 (10-H, s), 8.60 (20-H, s), 5.28 and 4.98 (15-1-CH2, dd), 4.38, 4.32, 4.22, 4.15 (7,8,17,18-H, all m), 3.85 (15~3-Me, s), 3.51 (21-Me, s), 3.18 (121-Me, s), 3.10 (32-Me, s 2.12-2.41 (171-CH2, m), 2.15-2.34 (81-CR2, m), 1.76-2.02 (172-CH2, m), 1.89 (71-Me, d), 1.61 (lδ^Me, d), 1.07 (82-Me, t). 3.82, 3.70,

3.20, 3.10, 2.78, 2.32, 1.90 (CH2‘s of homotaurine at C-131 and C-173)

Example 9. Palladium 31-(3-sulfopropylimino)-15-methoxycarbonylmethyl-Rhodo-bacteriochlorin 131,173-di(3-sulfopropyl)amide tripotassium salt (Compound 9)

Compound 9 was obtained from HPLC as a minor product during synthesis of 8.

Absorption spectrum (MeOH): 729 (1.00), 502 (0.10), 380 (0.69), 328 (0.57).

ESI-MS (30.4.2000): 1171 (M-K+H), 1153 (M–2K-H+Na), 1131 (M-2K), 566 ([M-K]/2), 364 ([M-3K]/3).

NMR (MeOH-d4): 8.71 (1H), 8.63 (1.5H), 8.23 (0.5H) (5-, 10- and 20-H, all-m), 5.30 and 4.88 (151-CH2, dd), 4.43 and 4.25 (7,8,17,18-H, m), 3.85 (15~3-Me, s), 3.31 (21-Me, s), 3.22 (121-Me, s), 3.17 (32-Me, m), 1.89-2.44 (171 and 172-CH2, m), 2.25 (81-CH2, m), 1.91 (71-Me, s), 1.64 (181– Me, s), 1.08 (82-Me, t), 4.12, 3.56, 3.22, 3.16, 2.80 and 2.68 (CH2‘s of homotaurine).

Example 10. Palladium 31-oxo-15-methoxycarbonylmethyl-Rhodobacteriochlorin 131-(2-sulfoethyl)amide, 173-(N-immunoglobulin G)amide potassium salt (Compound 13)

Ten (10) mg of compound 4 were reacted with 20 mg of sulfo-NHS and 15 mg of EDC in 1 ml of dry DMSO for 1 hour at room temperature, then rabbit IgG (0.6 mg) in PBS (2.5 ml) was added, and the mixture was further incubated overnight at room temperature. The mixture was evaporated to dryness, then re-dissolved in 1 ml of PBS and loaded on Sephadex G-25 column equilibrated with PBS. A colored band was eluted with 4-5 ml of PBS. The pigment/protein ratio in the obtained conjugate 13 was determined by optical density at 753 and 280 mn, respectively, and varied between 0.5/1 to 1/1 of pigment 13/protein.

Example 11. Preparation of palladium 31-oxo-15-methoxycarbonylmethyl-Rhodobacteriochlorin 131-(2-carboxyethyl)amide dipotassium salt (Compound

M)

The preparation and purification of the title compound 14 were carried out as described in Example 2, by reaction of compound 2 with 3-aminopropionic acid (β-alanine) (150 mg) instead of taurine. Yield: 85%.

Example 12. Preparation of palladium 31-oxo-15-methoxycarbonylmethyl-Rhodobacteriochlorin 131-(3-phosphopropyl)amide tripotassium salt (Compound

15)

The preparation and purification of the title compound 15 were carried out as described in Example 2, by reaction of compound 2 with 3 -amino- 1-propanephosphonic acid (180 mg) instead of taurine. Yield: 68%.

Example 13. Palladium 31-(3-sulfopropylamino)-15-methoxycarbonylmethyl-Rhodobacteriochlorin 131,173-di(3-sulfopropyl)amide tripotassium salt (Compound 16)

For reduction of the imine group in 31-(3-sulfopropylimino) to the correspondent 31-(3-sulfopropylamino) group, compound 9 (8 mg) was reacted by stirring with sodium cyanoborohydride (15 mg) in 5 ml of methanol overnight at room temperature. Then the reaction mixture was treated with 0.05 M HCl (5 ml), neutralized with 0.01 M KOH, and evaporated. The title product 16 was purified using HPLC conditions as described in Example 2. Yield: 80-90%).

PATENT
US 7947672

REFERENCES

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2: Betrouni N, Lopes R, Puech P, Colin P, Mordon S. A model to estimate the outcome of prostate cancer photodynamic therapy with TOOKAD Soluble WST11. Phys Med Biol. 2011 Aug 7;56(15):4771-83. Epub 2011 Jul 13. PubMed PMID: 21753234.

3: Chevalier S, Anidjar M, Scarlata E, Hamel L, Scherz A, Ficheux H, Borenstein N, Fiette L, Elhilali M. Preclinical study of the novel vascular occluding agent, WST11, for photodynamic therapy of the canine prostate. J Urol. 2011 Jul;186(1):302-9. Epub 2011 May 20. PubMed PMID: 21600602.

4: Dandler J, Wilhelm B, Scheer H. Photochemistry of bacteriochlorophylls in human blood plasma: 1. Pigment stability and light-induced modifications of lipoproteins. Photochem Photobiol. 2010 Mar-Apr;86(2):331-41. Epub 2009 Nov 23. PubMed PMID: 19947966.

5: Dandler J, Scheer H. Inhibition of aggregation of [Pd]-bacteriochlorophyllides in mesoporous silica. Langmuir. 2009 Oct 20;25(20):11988-92. PubMed PMID: 19772311.

6: Ashur I, Goldschmidt R, Pinkas I, Salomon Y, Szewczyk G, Sarna T, Scherz A. Photocatalytic generation of oxygen radicals by the water-soluble bacteriochlorophyll derivative WST11, noncovalently bound to serum albumin. J Phys Chem A. 2009 Jul 16;113(28):8027-37. PubMed PMID: 19545111.

7: Moore CM, Pendse D, Emberton M. Photodynamic therapy for prostate cancer–a review of current status and future promise. Nat Clin Pract Urol. 2009 Jan;6(1):18-30. Review. PubMed PMID: 19132003.

8: Preise D, Oren R, Glinert I, Kalchenko V, Jung S, Scherz A, Salomon Y. Systemic antitumor protection by vascular-targeted photodynamic therapy involves cellular and humoral immunity. Cancer Immunol Immunother. 2009 Jan;58(1):71-84. Epub 2008 May 17. PubMed PMID: 18488222.

9: Fleshker S, Preise D, Kalchenko V, Scherz A, Salomon Y. Prompt assessment of WST11-VTP outcome using luciferase transfected tumors enables second treatment and increase in overall therapeutic rate. Photochem Photobiol. 2008 Sep-Oct;84(5):1231-7. Epub 2008 Apr 8. PubMed PMID: 18399928.

10: Berdugo M, Bejjani RA, Valamanesh F, Savoldelli M, Jeanny JC, Blanc D, Ficheux H, Scherz A, Salomon Y, BenEzra D, Behar-Cohen F. Evaluation of the new photosensitizer Stakel (WST-11) for photodynamic choroidal vessel occlusion in rabbit and rat eyes. Invest Ophthalmol Vis Sci. 2008 Apr;49(4):1633-44. PubMed PMID: 18385085.

11: Fabre MA, Fuseau E, Ficheux H. Selection of dosing regimen with WST11 by Monte Carlo simulations, using PK data collected after single IV administration in healthy subjects and population PK modeling. J Pharm Sci. 2007 Dec;96(12):3444-56. PubMed PMID: 17854075.

12: Brandis A, Mazor O, Neumark E, Rosenbach-Belkin V, Salomon Y, Scherz A. Novel water-soluble bacteriochlorophyll derivatives for vascular-targeted photodynamic therapy: synthesis, solubility, phototoxicity and the effect of serum proteins. Photochem Photobiol. 2005 Jul-Aug;81(4):983-93. PubMed PMID: 15839743.

13: Mazor O, Brandis A, Plaks V, Neumark E, Rosenbach-Belkin V, Salomon Y, Scherz A. WST11, a novel water-soluble bacteriochlorophyll derivative; cellular uptake, pharmacokinetics, biodistribution and vascular-targeted photodynamic activity using melanoma tumors as a model. Photochem Photobiol. 2005 Mar-Apr;81(2):342-51. PubMed PMID: 15623318.

14: Plaks V, Posen Y, Mazor O, Brandis A, Scherz A, Salomon Y. Homologous adaptation to oxidative stress induced by the photosensitized Pd-bacteriochlorophyll derivative (WST11) in cultured endothelial cells. J Biol Chem. 2004 Oct 29;279(44):45713-20. Epub 2004 Aug 31. PubMed PMID: 15339936.

////////PADELIPORFIN,  WST11, WST-11, WST 11, Stakel, padeliporfin, palladiumbacteriopheophorbide monolysine taurine, EU 2017, EMA 2017

CCC1C(C2=NC1=CC3=C(C(=C([N-]3)C(=C4C(C(C(=N4)C=C5C(=C(C(=C2)[N-]5)C(=O)C)C)C)CCC(=O)O)CC(=O)OC)C(=O)NCCS(=O)(=O)O)C)C.[Pd+2]

Novel Drug Approvals for 2017, A Review/Compilation


CDSCOImage result for FDA EMA

DRUG APPROVALS BY DR ANTHONY MELVIN CRASTO, Novel Drug Approvals for 2017, A Review Compilation (USFDA, EMA, PMDA, CDSCO).

Any errors in this compilation, email  amcrasto@gmail.com, Call +919323115463

Some gaps will be filled up soon keep watching……………..

INDEX, NAME (click on the title,  it contains link)

SECTION A; USFDA Approvals

1 Abaloparatide

2 Abemaciclib

3 ACALABRUTINIB

4 ANGIOTENSIN II

5 AVELUMAB

6 BENRALIZUMAB

7 BENZNIDAZOLE

8 BETRIXABAN

9 BRIGATINIB

10 BRODALUMAB

11 CERLIPONASE ALPA

12 COPANLISIB

13 DEFLAZACORT

14 Delafloxacin

15 Deutetrabenazine

16DUPILUMAB

17 DURVALUMAB

18 EDAVARONE

19 EMICIZUMAB

20 Enasidenib

21 ERTUGLIFLOZIN

22 ETELCALCETIDE

23 GLECAPREVIR

24 GUSELKUMAB

25 INOTUZUMAB OZOGAMICIN

26 LATANOPROSTENE

27 LETERMOVIR

28 MACIMORELIN ACETATE

29 MEROPENEM

30 MIDOSTAURIN

31 NALDEMEDINE

32 NERATINIB

33 NETARSUDIL

34 NIRAPARIB

35 Ocrelizumab

36 OZENOXACIN

37 PIBRENTASVIR

38 PLECANATIDE

39 RIBOCICLIB

40  SARILUMAB

41 SECNIDAZOLE

42 SAFINAMIDE

43 SEMAGLUTIDE

44 SOFOSBUVIR

45 TELOTRISTAT ETHYL

46 VABORBACTAM

47 VALBENAZINE

48 VESTRONIDASE ALFA-VJBK

49 VELPATASVIR

50 VOXILAPREVIR

INDEX, FORMULATION NAME

USFDA

•Aliqopa (COPANLISIBto treat adults with relapsed follicular lymphoma — a slow-growing type of nonHodgkin lymphoma (a cancer of the lymph system) — who have received at least two prior systemic therapies;

• ALUNBRIG, BRIGATINIBTo treat patients with anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer (NSCLC) who have progressed on or are intolerant to crizotinib

• Austedo, Deutetrabenazine For the treatment of chorea associated with Huntington’s disease

• Bavencio (avelumab) for the treatment of patients 12 years and older with a rare and aggressive form of cancer called metastatic Merkel cell carcinoma, including those who have not received prior chemotherapy;

•BAXDELLA, Delafloxacin, BACTERIAL INFECTIONS

• Benznidazole to treat children ages 2 to 12 years with Chagas disease, a parasitic infection that can cause serious heart illness after years of infection, and can also affect swallowing and digestion. This is the first treatment approved in the United States for this rare disease;

• Besponsa (inotuzumab ozogamicin) for the treatment of adults with a type of cancer of the blood called relapsed or refractory B-cell precursor acute lymphoblastic leukemia;

BEVYXXA, BETRIXABAN, For the prophylaxis of venous thromboembolism (VTE) in adult patients hospitalized for an acute medical illness

• BRINEURA, CERLIPONASE ALFATo treat a specific form of Batten disease

• Calquence (ACALABRUTINIB) to treat adults with mantle cell lymphoma who have received at least one prior therapy. Mantle cell lymphoma is a particularly aggressive cancer;

• DUPIXENT, (DUPILUMAB) To treat adults with moderate-to-severe eczema (atopic dermatitis)

• Emflaza (deflazacort) to treat patients age 5 years and older with Duchenne muscular dystrophy, a rare genetic disorder that causes progressive muscle deterioration and weakness;

• FASENRA, BENRALIZUMAB, For add-on maintenance treatment of patients with severe asthma aged 12 years and older, and with an eosinophilic phenotype

• Giapreza (angiotensin II), for the treatment of hypotension in adults with distributive or vasodilatory shock (dangerously low blood pressure despite adequate heart function) whose blood pressure remains low despite receiving fluids and treatment with drugs called vasopressors;

•  HEMLIBRA EMICIZUMAB To prevent or reduce the frequency of bleeding episodes in adult and pediatric patients with hemophilia A who have developed antibodies called Factor VIII (FVIII) inhibitors.

• Idhifa (enasidenibfor the treatment of adults with relapsed or refractory acute myeloid leukemia, a form of blood cancer, who have a specific genetic mutation;

• IMFINZI, DURVALUMAB To treat patients with locally advanced or metastatic urothelial carcinoma

• Ingrezza (valbenazineto treat adults with tardive dyskinesia, a side effect of some antipsychotic medications whereby patients can experience uncontrollable stiff, jerky movements of their face and body, and other uncontrolled movements such as eye-blinking, sticking out the tongue, and arm-waving;

•  KEVZARA SARILUMAB, RHEUMATOID ARTHRITIS

• KISQALI, RIBOCICLIB, To treat postmenopausal women with a type of advanced breast cancer

• Macrilen  macimorelin acetate, For the diagnosis of adult growth hormone deficiency

• Mavyret (glecaprevir and pibrentasvir) to treat adults with chronic hepatitis C virus genotypes 1-6 without cirrhosis (liver disease) or with mild cirrhosis, including patients with moderate to severe kidney disease, as well as those who are on hemodialysis;

• Mepsevii (vestronidase alfa-vjbk) to treat patients with Sly syndrome or mucopolysaccharidosis type 7 – a rare genetic disorder where an enzyme deficiency results in skeletal abnormalities, developmental delay, enlarged liver and spleen, and narrowed airways, which can lead to respiratory infections;

 Nerlynx (neratinib) for the extended adjuvant treatment — a form of therapy administered after an initial treatment to further lower the risk of the cancer coming back — of early-stage, human epidermal growth factor receptor 2 (HER2)-positive breast cancer;

 OCREVUS, OCRELIZUMAB, To treat patients with relapsing and primary progressive forms of multiple sclerosis

 OZEMPIC SEMAGLUTIDE To improve glycemic control in adults with type 2 diabetes mellitus

PARSABIV, ETELCALCETIDE, To treat secondary hyperparathyroidism in adult patients with chronic kidney disease undergoing dialysis

• Prevymis (letermovir) for prevention of an infection called cytomegalovirus (CMV) in patients who are receiving a bone marrow transplant. CMV disease can cause serious health issues in these patients;

 Radicava (edaravoneto treat patients with amyotrophic lateral sclerosis, commonly referred to as Lou Gehrig’s disease, a rare disease that attacks and kills the nerve cells that control voluntary muscles;

• RHOPRESSA, NETARSUDIL To treat glaucoma or ocular hypertension

• Rydapt (midostaurin) to treat adults newly diagnosed with a form of blood cancer known as acute myeloid leukemia who have a specific genetic mutation called FLT3, in combination with chemotherapy;

• Siliq (brodalumab) to treat adults with moderate-to-severe plaque psoriasis, a chronic disorder in which the body’s immune system sends out faulty signals that speed growth of skin cells that then accumulate, causing red, flaky patches that can appear anywhere on the body;

•SOLOSEC, SECNIDAZOLE To treat bacterial vaginosis

•  STEGLATRO ERTUGLIFLOZIN To improve glycemic control in adults with type 2 diabetes mellitus

• Symproic (Naldemedine) for the treatment of opioid-induced constipation in adults with chronic noncancer pain; • Tremfya (guselkumab) for the treatment of adults with moderate-to-severe plaque psoriasis;

• Trulance (plecanatide) to treat adults with chronic idiopathic constipation, which is a persistent condition of constipation due to unknown origin;

• TYMLOS, Abaloparatide, To treat osteoporosis in postmenopausal women at high risk of fracture or those who have failed other therapies

• Vabomere (vaborbactam and meropenem) for treatment of adults with complicated urinary tract infections, including pyelonephritis (kidney infection) caused by bacteria;

• Verzenio (abemaciclib) to treat adults who have hormone receptor (HR)-positive, HER2-negative advanced or metastatic breast cancer that has progressed after taking therapy that alters a patient’s hormones (endocrine therapy);

• Vosevi (sofosbuvir/velpatasvir/voxilaprevir) to treat adults with chronic hepatitis C virus genotypes 1-6 without cirrhosis (liver disease) or with mild cirrhosis;

• VYZULTA LATANOPROSTENE To treat intraocular pressure in patients with open-angle glaucoma or ocular hypertension.

• Xadago (safinamide) as an add-on treatment for patients with Parkinson’s disease who are currently taking levodopa/carbidopa and experiencing “off” episodes;

XERMELO, TELOTRISTAT ETHYL combined with somatostatin analog (SSA) therapy to treat adults with carcinoid syndrome diarrhea that SSA therapy alone has inadequately controlled, and;

• XEPI OZENOXACIN TO TREAT IMPETIGO

XERMELO, TELOTRISTAT ETHYL, To treat carcinoid syndrome diarrhea

• Zejula (niraparib) for the maintenance treatment (intended to delay cancer growth) of adults with recurrent epithelial ovarian, fallopian tube or primary peritoneal cancer, whose tumors have completely or partially shrunk (complete or partial response, respectively) in response to platinum-based chemotherapy

USFDA

No. Drug
Name
Active Ingredient Approval Date FDA-approved use on approval date
46. Giapreza angiotensin II 12/21/2017

Press Release
Drug Trials Snapshot

To increase blood pressure in adults with septic or other distributive shock
45. Macrilen macimorelin acetate 12/20/2017

Drug Trials Snapshot

For the diagnosis of adult growth hormone deficiency
44. Steglatro ertugliflozin 12/19/2017

Drug Trials Snapshot

To improve glycemic control in adults with type 2 diabetes mellitus
43. Rhopressa netarsudil 12/18/2017

Drug Trials Snapshot

To treat glaucoma or ocular hypertension
42. Xepi ozenoxacin 12/11/2017 To treat impetigo
Drug Trials Snapshot
41. Ozempic semaglutide 12/5/2017

Drug Trials Snapshot

To improve glycemic control in adults with type 2 diabetes mellitus
40. Hemlibra emicizumab 11/16/2017

Press Release
Drug Trials Snapshot

To prevent or reduce the frequency of bleeding episodes in adult and pediatric patients with hemophilia A who have developed antibodies called Factor VIII (FVIII) inhibitors.
39. Mepsevii vestronidase alfa-vjbk 11/15/2017

Press Release
Drug Trials Snapshot

To treat pediatric and adult patients with an inherited metabolic condition called mucopolysaccharidosis type VII (MPS VII), also known as Sly syndrome.
38. Fasenra  benralizumab 11/14/2017 For add-on maintenance treatment of patients with severe asthma aged 12 years and older, and with an eosinophilic phenotype
Drug Trials Snapshot
37. Prevymis letermovir 11/8/2017 To prevent infection after bone marrow transplant
Drug Trials Snapshot
36. Vyzulta latanoprostene bunod ophthalmic solution 11/2/2017 To treat intraocular pressure in patients with open-angle glaucoma or ocular hypertension.
Drug Trials Snapshot
35. Calquence acalabrutinib 10/31/2017 To treat adults with mantle cell lymphoma
Press Release
Drug Trials Snapshot
34. Verzenio abemaciclib 9/28/2017 To treat certain advanced or metastatic breast cancers
Press Release
Drug Trials Snapshot
33. Solosec secnidazole 9/15/2017 To treat bacterial vaginosis
Drug Trials Snapshot
32. Aliqopa copanlisib 9/14/2017 To treat adults with relapsed follicular lymphoma
Press Release
Drug Trials Snapshot
31. benznidazole benznidazole 8/29/2017 To treat children ages 2 to 12 years old with Chagas disease
Press Release
Drug Trials Snapshot
30. Vabomere meropenem and vaborbactam 8/29/2017 To treat adults with complicated urinary tract infections
Press Release
Drug Trials Snapshot
29. Besponsa inotuzumab ozogamicin 8/17/2017 To treat adults with relapsed or refractory acute lymphoblastic leukemia
Press Release
Drug Trials Snapshot
28. Mavyret glecaprevir and pibrentasvir 8/3/2017 To treat adults with chronic hepatitis C virus
Press Release
Drug Trials Snapshot
27. Idhifa enasidenib 8/1/2017 To treat relapsed or refractory acute myeloid leukemia
Press Release
Drug Trials Snapshot
26. Vosevi sofosbuvirvelpatasvir and voxilaprevir 7/18/2017 To treat adults with chronic hepatitis C virus
Press Release
Drug Trials Snapshot
25. Nerlynx neratinib maleate 7/17/2017 To reduce the risk of breast cancer returning
Press Release
Drug Trials Snapshot
24. Tremfya guselkumab 7/13/2017 For the treatment of adult patients with moderate-to-severe plaque psoriasis
Drug Trials Snapshot
23. Bevyxxa betrixaban 6/23/2017 For the prophylaxis of venous thromboembolism (VTE) in adult patients hospitalized for an acute medical illness
Drug Trials Snapshot
22. Baxdela delafloxacin 6/19/2017 To treat patients with acute bacterial skin infections
Drug Trials Snapshot
21. Kevzara sarilumab 5/22/2017 To treat adult rheumatoid arthritis
Drug Trials Snapshot
20. Radicava edaravone 5/5/2017 To treat patients with amyotrophic lateral sclerosis (ALS)
Press Release
Drug Trials Snapshot
19. Imfinzi durvalumab 5/1/2017 To treat patients with locally advanced or metastatic urothelial carcinoma
Web Post
Drug Trials Snapshot
18. Tymlos abaloparatide 4/28/2017 To treat osteoporosis in postmenopausal women at high risk of fracture or those who have failed other therapies
Drug Trials Snapshot
17. Rydapt midostaurin 4/28/2017 To treat acute myeloid leukemia
Press Release Chemistry Review(s) (PDF)
Drug Trials Snapshot
16. Alunbrig brigatinib 4/28/2017 To treat patients with anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer (NSCLC) who have progressed on or are intolerant to crizotinib
Drug Trials Snapshot
15. Brineura cerliponase alfa 4/27/2017 To treat a specific form of Batten disease
Press Release
Drug Trials Snapshot
14. Ingrezza valbenazine 4/11/2017 To treat adults with tardive dyskinesia
Press Release Chemistry Review(s) (PDF)Drug Trials Snapshot
13. Austedo deutetrabenazine 4/3/2017 For the treatment of chorea associated with Huntington’s disease
Drug Trials Snapshot,  Chemistry Review(s) (PDF)
12. Ocrevus ocrelizumab 3/28/2017 To treat patients with relapsing and primary progressive forms of multiple sclerosis
Press Release
Drug Trials Snapshot
11. Dupixent dupilumab 3/28/2017 To treat adults with moderate-to-severe eczema (atopic dermatitis)
Press Release
Drug Trials Snapshot
10. Zejula niraparib 3/27/2017 For the maintenance treatment for recurrent epithelial ovarian, fallopian tube or primary peritoneal cancers
Press Release
Drug Trials Snapshot
9. Symproic naldemedine 3/23/2017

For the treatment of opioid-induced constipation
Drug Trials Snapshot

8. Bavencio avelumab 3/23/2017 To treat metastatic Merkel cell carcinoma
Press Release
Drug Trials Snapshot
7. Xadago safinamide 3/21/2017 To treat Parkinson’s disease
Press Release
Drug Trials SnapshotChemistry Review(s) (PDF)
6. Kisqali ribociclib 3/13/2017 To treat postmenopausal women with a type of advanced breast cancer
Drug Trials Snapshot
5. Xermelo telotristat ethyl 2/28/2017 To treat carcinoid syndrome diarrhea
Press Release
Drug Trials Snapshot
4. Siliq brodalumab 2/15/2017 To treat adults with moderate-to-severe plaque psoriasis
Press Release
Drug Trials Snapshot
3. Emflaza deflazacort 2/9/2017 To treat patients age 5 years and older with Duchenne muscular dystrophy (DMD)
Press Release
Drug Trials Snapshot
2. Parsabiv etelcalcetide 2/7/2017 To treat secondary hyperparathyroidism in adult patients with chronic kidney disease undergoing dialysis
Drug Trials Snapshot
1. Trulance plecanatide 1/19/2017 To treat Chronic Idiopathic Constipation (CIC) in adult patients.
Press Release
Drug Trials Snapshot

* This information is currently accurate. In rare instances, it may be necessary for FDA to change a drug’s new molecular entity (NME) designation or the status of its application as a novel new biologics license application (BLA).  For instance, new information may become available which could lead to a reconsideration of the original designation or status.  If changes must be made to a drug’s designation or the status of an application as a novel BLA, the Agency intends to communicate the nature of, and the reason for, any revisions as appropriate.

USFDA 2017
2017/12/21 Angiotensin II Giapreza La Jolla Pharmaceutical
2017/12/20 Ertugliflozin Steglatro Merck Sharp Dohme
2017/12/20 Macimorelin acetate Macrilen Aeterna Zentaris GmbH
2017/12/18 Netarsudil mesylate Rhopressa Aerie Pharmaceuticals
2017/12/11 Ozenoxacin Xepi Ferrer Internacional S.A.
2017/12/5 Semaglutide Ozempic Novo Nordisk Inc
2017/11/16 Emicizumab Hemlibra Genentech BLA
2017/11/15 Vestronidase alfa Mepsevii Ultragenyx Pharmaceutical BLA
2017/11/14 Benralizumab Fasenra AstraZeneca AB BLA
2017/11/8 Letermovir Prevymis Merck Sharp Dohme
2017/11/2 Latanoprostene bunod Vyzulta Bausch & Lomb Incorporated
2017/10/31 Acalabrutinib Calquence AstraZeneca Pharmaceuticals LP
2017/9/28 Abemaciclib Verzenio Eli Lilly
2017/9/15 Secnidazole Solosec Symbiomix Therapeutics
2017/9/14 Copanlisib Aliqopa Bayer Healthcare Pharmaceuticals
2017/8/29 Benznidazole Chemo Research
2017/8/29 Meropenem – Vaborbactam Vabomere Rempex Pharmaceuticals
2017/8/17 Inotuzumab ozogamicin Besponsa Wyeth Pharmaceuticals BLA
2017/8/3 Glecaprevir – Pibrentasvir Mavyret AbbVie
2017/8/1 Enasidenib Idhifa Celgene Corporation
2017/7/18 Sofosbuvir – Velpatasvir – Voxilaprevir Vosevi Gilead Sciences
2017/7/17 Neratinib maleate Nerlynx Puma Biotechnology
2017/7/13 Guselkumab Tremfya Janssen Biotech BLA
2017/6/23 Betrixaban Bevyxxa Portola Pharmaceuticals
2017/6/19 Delafloxacin meglumine Baxdela Melinta Therapeutics
2017/5/22 Sarilumab Kevzara Sanofi Synthelabo BLA
2017/5/5 Edaravone Radicava Mitsubishi Tanabe Pharma America
2017/5/1 Durvalumab Imfinzi AstraZeneca UK BLA
2017/4/28 Abaloparatide Tymlos Radius Health
2017/4/28 Midostaurin Rydapt Novartis Pharmaceuticals
2017/4/28 Brigatinib Alunbrig Ariad Pharmaceuticals
2017/4/27 Cerliponase alfa Brineura BioMarin Pharmaceutical BLA
2017/4/11 Valbenazine Ingrezza Neurocrine Biosciences
2017/4/3 Deutetrabenazine Austedo Teva Pharmaceuticals
2017/3/28 Ocrelizumab Ocrevus Genentech BLA
2017/3/28 Dupilumab Dupixent Regeneron Pharmaceuticals BLA
2017/3/27 Niraparib Zejula Tesaro
2017/3/23 Naldemedine tosylate Symproic Shionogi
2017/3/23 Avelumab Bavencio EMD Serono BLA
2017/3/23 Safinamide mesylate Xadago Newron Pharmaceuticals
2017/3/21 Ribociclib Kisqali Novartis Pharmaceuticals
2017/2/28 Telotristat ethyl Xermelo Lexicon Pharmaceuticals
2017/2/15 Brodalumab Siliq Valeant Pharmaceuticals BLA
2017/2/9 Deflazacort Emflaza Marathon Pharmaceuticals
2017/2/8 Etelcalcetide hydrochloride Parsavib KAI Pharmaceuticals
2017/1/19 Plecanatide Trulance Synergy Pharmaceuticals

1 Abaloparatide

RADIUS

str1

Tymlos

FDA 4/28/2017

To treat osteoporosis in postmenopausal women at high risk of fracture or those who have failed other therapies
Drug Trials Snapshot

Image result for AbaloparatideImage result for Abaloparatide

link……..https://newdrugapprovals.org/2018/02/13/abaloparatide-%D0%B0%D0%B1%D0%B0%D0%BB%D0%BE%D0%BF%D0%B0%D1%80%D0%B0%D1%82%D0%B8%D0%B4-%D8%A3%D8%A8%D8%A7%D9%84%D9%88%D8%A8%D8%A7%D8%B1%D8%A7%D8%AA%D9%8A%D8%AF-%E5%B7%B4%E7%BD%97%E6%97%81/

2 Abemaciclib

ELI LILLY

Verzenio abemaciclib FDA 9/28/2017 To treat certain advanced or metastatic breast cancers
Press Release
Drug Trials Snapshot

LINK https://newdrugapprovals.org/2015/10/19/abemaciclib-bemaciclib/

Image result for abemaciclibImage result for abemaciclib

3 Acalabrutinib

Calquence FDA APPROVED

10/31/2017

To treat adults with mantle cell lymphoma
Press Release
Drug Trials Snapshot

Image result for AcalabrutinibImage result for AcalabrutinibImage result for Acalabrutinib

LINK……….https://newdrugapprovals.org/2018/02/02/acalabrutinib-acp-196-%D0%B0%D0%BA%D0%B0%D0%BB%D0%B0%D0%B1%D1%80%D1%83%D1%82%D0%B8%D0%BD%D0%B8%D0%B1-%D8%A3%D9%83%D8%A7%D9%84%D8%A7%D8%A8%D8%B1%D9%88%D8%AA%D9%8A%D9%86%D9%8A%D8%A8-%E9%98%BF/

4 Angiotensin II

LA JOLLA

Giapreza angiotensin II 12/21/2017 To increase blood pressure in adults with septic or other distributive shock
Press Release
Drug Trials Snapshot

Image result for angiotensin IIImage result for GIAPREZA

LINK https://newdrugapprovals.org/2017/12/22/fda-approves-drug-giapreza-angiotensin-ii-to-treat-dangerously-low-blood-pressure/

5 AVELUMAB

MERCK

Image result for AVELUMABImage result for AVELUMAB

Bavencio FDA 3/23/2017 To treat metastatic Merkel cell carcinoma
Press Release
Drug Trials Snapshot

LINK…..https://newdrugapprovals.org/2017/03/24/fda-approves-first-treatment-bavencio-avelumabfor-rare-form-of-skin-cancer/

6 BENRALIZUMAB

ASTRA ZENECA

Fasenra benralizumab

FDA 11/14/2017

For add-on maintenance treatment of patients with severe asthma aged 12 years and older, and with an eosinophilic phenotype
Drug Trials Snapshot

Image result for BENRALIZUMAB

7 Benznidazole

CHEMO RESEARCH

Image result for BENZNIDAZOLE

Image result for BENZNIDAZOLEImage result for BENZNIDAZOLE

benznidazole FDA

8/29/2017

To treat children ages 2 to 12 years old with Chagas disease
Press Release
Drug Trials Snapshot

LINK…https://newdrugapprovals.org/2017/08/30/fda-approves-first-u-s-treatment-benznidazole-for-chagas-disease/

8 BETRIXABAN

PORTOLA PHARMA

Image result for betrixaban

Bevyxxa FDA

6/23/2017

For the prophylaxis of venous thromboembolism (VTE) in adult patients hospitalized for an acute medical illness
Drug Trials Snapshot

Image result for betrixabanImage result for betrixaban

STR2STR1

LINK…….https://newdrugapprovals.org/2013/03/05/phase-3-portola-pharma-betrixaban-long-acting-oral-direct-factor-xa-inhibitor/

9 BRIGATINIB

Figure imgf000127_0001

TAKEDA

Image result for BRIGATINIBImage result for BRIGATINIB

Alunbrig FDA

4/28/2017

To treat patients with anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer (NSCLC) who have progressed on or are intolerant to crizotinib
Drug Trials Snapshot

LINK..https://newdrugapprovals.org/2017/01/20/brigatinib-%D0%B1%D1%80%D0%B8%D0%B3%D0%B0%D1%82%D0%B8%D0%BD%D0%B8%D0%B1-%D8%A8%D8%B1%D9%8A%D8%BA%D8%A7%D8%AA%D9%8A%D9%86%D9%8A%D8%A8-%E5%B8%83%E6%A0%BC%E6%9B%BF%E5%B0%BC/

10 BRODALUMAB

VALEANT PHARMA

Siliq FDA

2/15/2017

To treat adults with moderate-to-severe plaque psoriasis
Press Release
Drug Trials Snapshot

Image result for BRODALUMAB

LINK ,,,,https://newdrugapprovals.org/2017/02/16/fda-approves-new-psoriasis-drug-siliq-brodalumab/

11 CERLIPONASE ALFA

Image resultImage result for cerliponase alfaImage result for cerliponase alfa

Brineura FDA 4/27/2017 To treat a specific form of Batten disease
Press Release
Drug Trials Snapshot

LINK….https://newdrugapprovals.org/2017/04/28/fda-approves-first-treatment-for-a-form-of-batten-disease-brineura-cerliponase-alfa/

12 Copanlisib

Aliqopa FDA APPROVED

9/14/2017

To treat adults with relapsed follicular lymphoma
Press Release
Drug Trials Snapshot

Copanlisib dihydrochloride.png

Image result for copanlisibImage result for copanlisib

LINK…..https://newdrugapprovals.org/2017/11/20/copanlisib/

13  DEFLAZACORT

MARATHON PHARMA

Image result for deflazacort

Emflaza FDA 2/9/2017 To treat patients age 5 years and older with Duchenne muscular dystrophy (DMD)
Press Release
Drug Trials Snapshot

LINK……https://newdrugapprovals.org/2017/02/17/deflazacort/

14 DELAFLOXACIN

Baxdela FDA APPROVED

6/19/2017

To treat patients with acute bacterial skin infections

Image result for delafloxacin

Image result for delafloxacinImage result for delafloxacin

LINK……..https://newdrugapprovals.org/2018/01/25/delafloxacin/

15 Deutetrabenazine

TEVA

Deutetrabenazine.svg

Image result for deutetrabenazineImage result for deutetrabenazineImage result for deutetrabenazine

LINK……………https://newdrugapprovals.org/2015/08/15/sd-809-deutetrabenazine-nda-submitted-by-teva/

Austedo FDA 4/3/2017 For the treatment of chorea associated with Huntington’s disease
Drug Trials Snapshot   Chemistry Review(s) (PDF)

STR1STR2str3

16 DUPILUMAB

SANOFI/REGENERON

Image result for DUPILUMABImage result for DUPILUMAB

Dupixent FDA 3/28/2017 To treat adults with moderate-to-severe eczema (atopic dermatitis)
Press Release
Drug Trials Snapshot

LINK…….https://newdrugapprovals.org/2017/03/29/fda-approves-new-eczema-drug-dupixent-dupilumab/

17 DURVALUMAB

ASTRA ZENECA

Image result for DURVALUMAB

Imfinzi

durvalumab FDA 5/1/2017To treat patients with locally advanced or metastatic urothelial carcinoma
Web Post
Drug Trials Snapshot

18 EDAVARONE

Image result for EDARAVONE

MITSUBISHI TANABE

Radicava FDA 5/5/2017 To treat patients with amyotrophic lateral sclerosis (ALS)
Press Release
Drug Trials Snapshot

Image result for EDARAVONEImage result for EDARAVONE

LINK………https://newdrugapprovals.org/2017/05/06/fda-approves-drug-to-treat-als-radicava-edaravone-%D1%8D%D0%B4%D0%B0%D1%80%D0%B0%D0%B2%D0%BE%D0%BD-%D8%A5%D9%8A%D8%AF%D8%A7%D8%B1%D8%A7%D9%81%D9%88%D9%86-%E4%BE%9D%E8%BE%BE%E6%8B%89%E5%A5%89/

19 EMICIZUMAB

ROCHE

Image result for EMICIZUMAB

Hemlibra emicizumab FDA 11/16/2017 To prevent or reduce the frequency of bleeding episodes in adult and pediatric patients with hemophilia A who have developed antibodies called Factor VIII (FVIII) inhibitors.
Press Release

Drug Trials Snapshot

LINK https://newdrugapprovals.org/2017/11/17/fda-approves-new-treatment-hemlibra-emicizumab-kxwh-to-prevent-bleeding-in-certain-patients-with-hemophilia-a/

Image result for EMICIZUMAB

20 Enasidenib

Enasidenib.png

Image result for EnasidenibImage result for Enasidenib

Idhifa FDA

8/1/2017

To treat relapsed or refractory acute myeloid leukemia
Press Release
Drug Trials Snapshot

Image result for Enasidenib

LINK……https://newdrugapprovals.org/2017/08/02/enasidenib-%D1%8D%D0%BD%D0%B0%D1%81%D0%B8%D0%B4%D0%B5%D0%BD%D0%B8%D0%B1-%D8%A5%D9%8A%D9%86%D8%A7%D8%B3%D9%8A%D8%AF%D9%8A%D9%86%D9%8A%D8%A8-%E4%BC%8A%E9%82%A3%E5%B0%BC%E5%B8%83/

21 Ertugliflozin

MERCK

Image result for ERTUGLIFLOZIN

Steglatro ertugliflozin FDA

12/19/2017

To improve glycemic control in adults with type 2 diabetes mellitus
Drug Trials Snapshot

LINK https://newdrugapprovals.org/2014/02/10/ertugliflozin/

Image result for ERTUGLIFLOZIN

22 ETELCALCETIDE

Amgen

Parsabiv FDA APPROVED

2/7/2017

To treat secondary hyperparathyroidism in adult patients with chronic kidney disease undergoing dialysis
Drug Trials SnapshotSYNTHESIS LINK……..https://cen.acs.org/articles/96/i4/the-year-in-new-drugs-2018.html

Image result for ETELCALCETIDEImage result for ETELCALCETIDE

SYNTHESIS LINK……..https://cen.acs.org/articles/96/i4/the-year-in-new-drugs-2018.html

23 GLECAPREVIR

ABBVIE

Image result for GLECAPREVIR

Mavyret glecaprevir and pibrentasvir FDA 8/3/2017 To treat adults with chronic hepatitis C virus
Press Release
Drug Trials Snapshot

LINK https://newdrugapprovals.org/2016/10/05/glecaprevir-abt-493/

Image result for GLECAPREVIRImage result for GLECAPREVIRImage result for GLECAPREVIR

24 GUSELKUMAB

JOHNSON AND JOHNSON

Tremfya

guselkumab

FDA 7/13/2017

For the treatment of adult patients with moderate-to-severe plaque psoriasis
Drug Trials Snapshot

Image result for GUSELKUMABImage result for GUSELKUMAB

25 Inotuzumab ozogamicin

PFIZER

Image result for inotuzumab ozogamicin

Image result for inotuzumab ozogamicinImage result for inotuzumab ozogamicin

Besponsa FDA

8/17/2017

To treat adults with relapsed or refractory acute lymphoblastic leukemia
Press Release
Drug Trials Snapshot

LINK….https://newdrugapprovals.org/2015/10/23/fda-grants-breakthrough-status-for-pfizers-leukaemia-drug-inotuzumab-ozogamicin/

26 LATANOPROSTENE

VALEANT

Image result for LATANOPROSTENE

latanoprostene bunod ophthalmic solution

FDA 11/2/2017

To treat intraocular pressure in patients with open-angle glaucoma or ocular hypertension.
Drug Trials Snapshot

Image result for LATANOPROSTENE

LINK https://newdrugapprovals.org/2014/09/27/nicox-stock-leaps-on-positive-ph-iii-glaucoma-drug-data-%E8%8B%B1%E6%96%87%E5%90%8D%E7%A7%B0/

27 LETERMOVIR

MERCK

Image result for LETERMOVIR

Prevymis FDA 11/8/2017 To prevent infection after bone marrow transplant
Drug Trials Snapshot

LINK https://newdrugapprovals.org/2016/05/16/letermovir-aic-246/

Image result for LETERMOVIRImage result for LETERMOVIR

 

28 Macimorelin acetate

AETERNA ZENTARIS

Macrilen macimorelin acetate FDA

12/20/2017

For the diagnosis of adult growth hormone deficiency
Drug Trials Snapshot

LINK https://newdrugapprovals.org/2014/01/07/aeterna-zentaris-submits-new-drug-application-to-fda-for-macimorelin-acetate-aezs-130-for-evaluation-of-aghd-2/

 Image result for macimorelin acetate

29 MEROPENEM

Image result for MEROPENEM


30 MIDOSTAURIN

NOVARTIS

Image result for MIDOSTAURIN

Rydapt FDA

4/28/2017

To treat acute myeloid leukemia
Press Release
Drug Trials Snapshot

STR1 STR2

LINK…….https://newdrugapprovals.org/2017/04/29/fda-approves-new-combination-treatment-for-acute-myeloid-leukemia-rydapt-midostaurin/

31 Naldemedine

FDA 3/23/2017, Symproic, For the treatment of opioid-induced constipation

Image result for naldemedine

Image result for naldemedineImage result for naldemedine

LINK……..https://newdrugapprovals.org/2018/01/24/naldemedine-%E3%83%8A%E3%83%AB%E3%83%87%E3%83%A1%E3%82%B8%E3%83%B3%E3%83%88%E3%82%B7%E3%83%AB%E9%85%B8%E5%A1%A9/

32 NERATINIB MALEATE

PUMA BIOTECH

Image result for NERATINIB

Image result for NERATINIBImage result for NERATINIBImage result for NERATINIB

Nerlynx FDA 7/17/2017 To reduce the risk of breast cancer returning
Press Release
Drug Trials Snapshot

LINK…https://newdrugapprovals.org/2014/04/11/neratinib-hki-272-puma-presents-positive-results-from-phase-ii-trial-of-its-investigational-drug-pb272/

33 NETARSUDIL

Rhopressa FDA APPROVED

12/18/2017

To treat glaucoma or ocular hypertension

Image result for Netarsudil

Image result for Netarsudil

LINK……https://newdrugapprovals.org/2018/01/29/netarsudil/

34 NIRAPARIB

TESARO

Zejula FDA 3/27/2017 For the maintenance treatment for recurrent epithelial ovarian, fallopian tube or primary peritoneal cancers
Press Release
Drug Trials Snapshot

Figure imgf000023_0001Image result for TESARO

Image result for NIRAPARIB

LINK…https://newdrugapprovals.org/2016/12/22/niraparib-mk-4827/

35 OCRELIZUMAB

ROCHE

Ocrevus FDA 3/28/2017 To treat patients with relapsing and primary progressive forms of multiple sclerosis
Press Release
Drug Trials Snapshot

Image result for ocrelizumabImage result for ocrelizumab

LINK..https://newdrugapprovals.org/2017/03/30/fda-approves-new-drug-to-treat-multiple-sclerosis-ocrevus-ocrelizumab/

36 OZENOXACIN

MEDIMETRIX

Image result for ozenoxacin

LINK https://newdrugapprovals.org/2014/03/28/ozenoxacin-in-phase-3-topical-formulation-in-the-treatment-of-impetigo/

Image result for ozenoxacin

Xepi ozenoxacin FDA

12/11/2017

To treat impetigo
Drug Trials Snapshot

37 Pibrentasvir

ABBVIE

Image result for PIBRENTASVIR

Mavyret glecaprevir and pibrentasvir FDA 8/3/2017 To treat adults with chronic hepatitis C virus
Press Release
Drug Trials Snapshot

LINK https://newdrugapprovals.org/2016/06/08/abt-530-pibrentasvir/

Image result for PIBRENTASVIRImage result for PIBRENTASVIR

38 PLECANATIDE

Plecanatide 普卡那肽 ليكاناتيد плеканатид

SYNERGY PHARMA

Image result for PLECANATIDEImage result for PLECANATIDE

Trulance FDA APPROVED

1/19/2017

To treat Chronic Idiopathic Constipation (CIC) in adult patients.
Press Release
Drug Trials Snapshot

LINK ….https://newdrugapprovals.org/2016/04/21/plecanatide-%E6%99%AE%E5%8D%A1%E9%82%A3%E8%82%BD-%D9%84%D9%8A%D9%83%D8%A7%D9%86%D8%A7%D8%AA%D9%8A%D8%AF-%D0%BF%D0%BB%D0%B5%D0%BA%D0%B0%D0%BD%D0%B0%D1%82%D0%B8%D0%B4/

39 RIBOCICLIB

NOVARTIS

2D chemical structure of 1374639-75-4

Structure..link for correct structure

Kisqali FDA 3/13/2017 To treat postmenopausal women with a type of advanced breast cancer
Drug Trials Snapshot

Image result for RIBOCICLIB

LINK https://newdrugapprovals.org/2015/10/19/ribociclib/

40  SARILUMAB

SANOFI /REGENERON

Kevzara sarilumab FDA 5/22/2017 To treat adult rheumatoid arthritis
Drug Trials Snapshot

LINK https://newdrugapprovals.org/2013/11/25/late-stage-success-for-sanofiregeneron-ra-drug-sarilumab/

Image result for SARILUMABImage result for SARILUMAB

41 SECNIDAZOLE

SYMBIOMIX

Secnidazole.svg

Solosec FDA 9/15/2017 To treat bacterial vaginosis
Drug Trials Snapshot

Image result for SECNIDAZOLE

link….https://newdrugapprovals.org/2017/11/03/secnidazole-%D1%81%D0%B5%D0%BA%D0%BD%D0%B8%D0%B4%D0%B0%D0%B7%D0%BE%D0%BB-%D8%B3%D9%8A%D9%83%D9%86%D9%8A%D8%AF%D8%A7%D8%B2%D9%88%D9%84-%E5%A1%9E%E5%85%8B%E7%A1%9D%E5%94%91/

42 SAFINAMIDE

NEWRON PHARMA

Image result for safinamide

Image result for safinamideImage result for safinamide

STR1

Xadago FDA 3/21/2017 To treat Parkinson’s disease
Press Release
Drug Trials Snapshot

LINK…https://newdrugapprovals.org/2017/03/22/fda-approves-drug-xadago-safinamide-%D1%81%D0%B0%D1%84%D0%B8%D0%BD%D0%B0%D0%BC%D0%B8%D0%B4-%D8%B3%D8%A7%D9%81%D9%8A%D9%86%D8%A7%D9%85%D9%8A%D8%AF-%E6%B2%99%E9%9D%9E%E8%83%BA-to-treat-parkins/

43 Semaglutide

NOVO NORDISK

Image result for SEMAGLUTIDE

Ozempic semaglutide FDA

12/5/2017

To improve glycemic control in adults with type 2 diabetes mellitus
Drug Trials Snapshot

LINK https://newdrugapprovals.org/2013/07/22/a-survey-of-promising-late-stage-diabetes-drugs/

Image result for SEMAGLUTIDE

44 SOFOSBUVIR

LINK https://newdrugapprovals.org/2013/12/11/us-approves-breakthrough-hepatitis-c-drug-sofosbuvir-all-about-drugs/

45 TELOTRISTAT ETHYL

LEXICON

LX1606 Hippurate.png

Xermelo FDA

2/28/2017

To treat carcinoid syndrome diarrhea
Press Release
Drug Trials Snapshot

Image result for Lexicon Pharmaceuticals, Inc.STR1

46 VABORBACTAM

THE MEDICINES CO

Image result for Vaborbactam

Vabomere meropenem and vaborbactam FDA

8/29/2017

To treat adults with complicated urinary tract infections
Press Release
Drug Trials Snapshot

Image result for VABOMERE

LINK     https://newdrugapprovals.org/2017/09/05/vaborbactam-%D0%B2%D0%B0%D0%B1%D0%BE%D1%80%D0%B1%D0%B0%D0%BA%D1%82%D0%B0%D0%BC-%D9%81%D8%A7%D8%A8%D9%88%D8%B1%D8%A8%D8%A7%D9%83%D8%AA%D8%A7%D9%85-%E6%B3%95%E7%A1%BC%E5%B7%B4%E5%9D%A6/

47 VALBENAZINE

NEUROCRINE

Image result for valbenazine

Image result for VALBENAZINEImage result for VALBENAZINEImage result for VALBENAZINE

Ingrezza FDA

4/11/2017

To treat adults with tardive dyskinesia
Press Release
Drug Trials Snapshot

LINK…………..https://newdrugapprovals.org/2017/04/12/fda-approves-first-drug-ingrezza-valbenazine-to-treat-tardive-dyskinesia/

48 Vestronidase alfa-vjbk

ULTRAGENYX

Mepsevii vestronidase alfa-vjbk FDA 11/15/2017 To treat pediatric and adult patients with an inherited metabolic condition called mucopolysaccharidosis type VII (MPS VII), also known as Sly syndrome.
Press Release
Drug Trials Snapshot

Image result for vestronidase alfa-vjbkImage result for vestronidase alfa-vjbk

LINK…https://newdrugapprovals.org/2017/11/16/fda-approves-mepsevii-vestronidase-alfa-vjbk-for-treatment-for-rare-genetic-enzyme-disorder/

49 VELPATASVIR

LINK https://newdrugapprovals.org/2016/07/30/velpatasvir-gs-5816-gilead-sciences-%D0%B2%D0%B5%D0%BB%D0%BF%D0%B0%D1%82%D0%B0%D1%81%D0%B2%D0%B8%D1%80-%D9%81%D8%A7%D9%84%D8%A8%D8%A7%D8%AA%D8%A7%D8%B3%D9%81%D9%8A%D8%B1-%E7%BB%B4%E5%B8%95/

50 VOXILAPREVIR

GILEAD

Image result for VOXILAPREVIR

Image result for VOXILAPREVIR

Vosevi sofosbuvir, velpatasvir and voxilaprevir FDA 7/18/2017 To treat adults with chronic hepatitis C virus
Press Release
Drug Trials Snapshot

LINK https://newdrugapprovals.org/2017/07/19/voxilaprevir-%D9%81%D9%88%D9%83%D8%B3%D9%8A%D9%84%D8%A7%D8%A8%D8%B1%D9%8A%D9%81%D9%8A%D8%B1-%E4%BC%8F%E8%A5%BF%E7%91%9E%E9%9F%A6-%D0%B2%D0%BE%D0%BA%D1%81%D0%B8%D0%BB%D0%B0%D0%BF%D1%80%D0%B5%D0%B2/

SECTION B; EMA approvals

European Medicines Agency’s – Human medicines: Highlights of 2017

Advances in medicines authorizations are essential for public health as they have the potential to improve treatment of diseases. In 2017, EMA recommended 92 medicines for marketing authorization. Of these, 35 had a new active substance, which has never been authorized in the European Union (EU) before. Many of these medicines represent a significant improvement in their therapeutic areas; they include medicines for children, for rare diseases and advanced therapies42. Amongst the 35 new active substances (NAS) that EMA recommended, 11 were new drugs and biologics to treat cancer, 05 to treat neurological disorders, 04 for infectious diseases, 04 for immunology/rheumatology, 03 for endocrinology, 02 each for Uro-nephrology, haematology, and dermatology, 01 for Pneumonology, and 01 for hepatology/gastroenterology class of drugs.

STR1 STR2 str3 str4 str5

STR1 STR2

EUROPE

2017/11/16 Niraparib Zejula Tesaro UK Limited O NME
2017/11/10 Adalimumab Cyltezo Boehringer Ingelheim International GmbH B
2017/11/10 Miglustat Miglustat Gen.Orph Gen.Orph G
2017/11/10 Ritonavir Ritonavir Mylan MYLAN S.A.S G
2017/11/10 Padeliporfin Tookad STEBA Biotech S.A
2017/11/10 Guselkumab Tremfya Janssen-Cilag International N.V. BLA
2017/9/27 Dupilumab Dupixent sanofi-aventis groupe BLA
2017/9/21 Darunavir / Cobicistat / Emtricitabine / Tenofovir alafenamide Symtuza Janssen-Cilag International N.V.
2017/9/21 Atezolizumab Tecentriq Roche Registration Limited BLA
2017/9/18 Avelumab Bavencio Merck Serono Europe Limited O BLA
2017/9/18 Entecavir Entecavir Mylan Mylan S.A.S G
2017/9/18 Lacosamide Lacosamide Accord Accord Healthcare Ltd G
2017/9/18 Midostaurin Rydapt Novartis Europharm Ltd O NME
2017/9/18 Telotristat ethyl Xermelo Ipsen Pharma O NME
2017/9/5 Trientine Cuprior GMP-Orphan SA
2017/9/5 Efavirenz / Emtricitabine / Tenofovir disoproxil Efavirenz/Emtricitabine/Tenofovir disoproxil Mylan Mylan S.A.S G
2017/8/24 Tivozanib hydrochloride monohydrate Fotivda EUSA Pharma (UK) Limited NME
2017/8/24 Adalimumab Imraldi Samsung Bioepis UK Limited (SBUK) B
2017/8/24 Nitisinone Nitisinone MDK (previously Nitisinone MendeliKABS) MendeliKABS Europe Ltd G
2017/8/22 Ribociclib Kisqali Novartis Europharm Ltd NME
2017/8/22 Cladribine Mavenclad Merck Serono Europe Limited
2017/7/26 Glecaprevir / Pibrentasvir Maviret AbbVie Limited NME
2017/7/26 Sofosbuvir / Velpatasvir / Voxilaprevi Vosevi Gilead Sciences International Ltd NME
2017/7/19 Insulin lispro Insulin lispro Sanofi sanofi-aventis groupe B
2017/7/19 Patiromer sorbitex calcium Veltassa Vifor Fresenius Medical Care Renal Pharma France NME
2017/7/17 Efavirenz / Emtricitabine / Tenofovir disoproxil Efavirenz/Emtricitabine/Tenofovir disoproxil Zentiva Zentiva k.s. G
2017/7/17 Brodalumab Kyntheum LEO Pharma A/S BLA
2017/7/17 beclometasone / formoterol / glycopyrronium bromide Trimbow Chiesi Farmaceutici S.p.A.
2017/7/13 Rituximab Blitzima Celltrion Healthcare Hungary Kft. B
2017/7/13 Cariprazine Reagila Gedeon Richter
2017/7/10 Spheroids of human autologous matrix-associated chondrocytes Spherox CO.DON AG
2017/7/6 Cenegermin Oxervate Dompe farmaceutici s.p.a. O BLA
2017/6/29 Inotuzumab ozogamicin Besponsa Pfizer Limited O BLA
2017/6/23 Etanercept Erelzi Sandoz GmbH
2017/6/23 Sarilumab Kevzara Sanofi-Aventis Groupe NME
2017/6/23 Dimethyl fumarate Skilarence Almirall S.A
2017/6/23 Carglumic acid Ucedane Lucane Pharma G
2017/6/15 Rituximab Rixathon, Riximyo B Sandoz GmbH
2017/6/2 Pentosan polysulfate sodium Elmiron bene-Arzneimittel GmbH
2017/6/2 Nonacog beta pegol Refixia Novo Nordisk A/S BLA
2017/5/30 Cerliponase alfa Brineura BioMarin International Limited O E BLA
2017/5/30 Nusinersen Spinraza Biogen Idec Ltd O NME
2017/5/24 Meningococcal group b vaccine (recombinant, adsorbed) Trumenba Pfizer Limited
2017/5/22 Ivabradine Ivabradine Accord Accord Healthcare Ltd G
2017/5/8 Dinutuximab beta Dinutuximab beta Apeiron Apeiron Biologics AG O E
2017/4/28 Emtricitabine – tenofovir disoproxil mixt Emtricitabine/Tenofovir disoproxil Krka d.d. KRKA, d.d., Novo mesto G
2017/4/24 Parathyroid hormone Natpar Shire Pharmaceuticals Ireland Ltd O C BLA
2017/4/20 Edoxaban Roteas Daiichi Sankyo Europe GmbH
2017/3/22 Tofacitinib citrate Xeljanz Pfizer Limited NME
2017/3/20 Umeclidinium Rolufta GlaxoSmithKline Trading Services Limited
2017/3/3 Chlormethine Ledaga Actelion Registration Ltd. O
2017/2/27 Pregabalin Pregabalin Zentiva Zentiva k.s. G
2017/2/17 Rituximab Truxima Celltrion Healthcare Hungary Kft. B
2017/2/13 Etanercept Lifmior Pfizer Limited
2017/2/13 Baricitinib Olumiant Eli Lilly Nederland B.V. NME
2017/1/19 Mercaptamine Cystadrops Orphan Europe S.A.R.L. O
2017/1/18 Bezlotoxumab Zinplava Merck Sharp & Dohme Limited NME
2017/1/11 Teriparatide Movymia STADA Arzneimittel AG B
2017/1/11 Insulin glargine / lixisenatide Suliqua Sanofi-Aventis Groupe
2017/1/9 Insulin aspart Fiasp Novo Nordisk A/S
2017/1/9 Tadalafil Tadalafil Mylan S.A.S G
2017/1/9 Tenofovir alafenamide Vemlidy Gilead Sciences International Ltd
2017/1/4 Lonoctocog alfa Afstyla CSL Behring GmbH BLA
2017/1/4 Darunavir Darunavir Mylan Mylan S.A.S. G
2017/1/4 Insulin glargine Lusduna Merck Sharp & Dohme Limited B
2017/1/4 Teriparatide Terrosa Gedeon Richter Plc. B

SECTION B; EMA Approvals

Combined drugs  USFDA+EMA +PMDA  list are listed below. trying to simplify search

1 Abaloparatide   USFDA

2 Abemaciclib  USFDA

3 ACALABRUTINIB USFDA

3A ALOFISEL        EMA

3B AMENAMEVIR  JAPAN

4 ANGIOTENSIN II USFDA

4A Atezolizumab            EMA

5 AVELUMAB      USFDA+EMA

6 BENRALIZUMAB     USFDA+EMA

6A BARICITINIB   JAPAN

7 BENZNIDAZOLE USFDA

8 BETRIXABAN USFDA

9 BRIGATINIB USFDA

10 BRODALUMAB    USFDA+EMA

10A BUROSUMAB           EMA

10B CARIPRAZINE HYDROCHLORIDE        EMA

11 CERLIPONASE ALPA    USFDA+EMA

12 COPANLISIB USFDA

13 DEFLAZACORT USFDA

14 Delafloxacin USFDA

15 Deutetrabenazine USFDA

16DUPILUMAB    USFDA+EMA

17 DURVALUMAB   USFDA

18 EDAVARONE   USFDA

19 EMICIZUMAB USFDA

20 Enasidenib USFDA

21 ERTUGLIFLOZIN USFDA

22 ETELCALCETIDE USFDA

22A FORODESINE   JAPAN

22B FLUCICLOVINE  EMA

23 GLECAPREVIR    USFDA+EMA

24 GUSELKUMAB    USFDA+EMA

25 INOTUZUMAB OZOGAMICIN     USFDA+EMA

26 LATANOPROSTENE USFDA

27 LETERMOVIR    USFDA+EMA

27A Utetium lu 177 dotatate        EMA

28 MACIMORELIN ACETATE USFDA

29 MEROPENEM USFDA

30 MIDOSTAURIN     USFDA+EMA

31 NALDEMEDINE USFDA

32 NERATINIB USFDA

33 NETARSUDIL USFDA

34 NIRAPARIB    USFDA+EMA

34A NONACOG        EMA

34B NUCINERSEN        EMA   +Japan

35 Ocrelizumab    USFDA+EMA

35A OXERVATE         EMA

36 OZENOXACIN USFDA

36A PATIROMER        EMA

36B PADELIPORFIN        EMA

36C PEMAFIBRATE  JAPAN

37 PIBRENTASVIR     USFDA+EMA

38 PLECANATIDE USFDA

38A PRALATREXATE    JAPAN

39 RIBOCICLIB      USFDA+EMA

39A ROLAPITANT         EMA

39BRURLOCTOCOG        EMA

40  SARILUMAB    USFDA+EMA

41 SECNIDAZOLE USFDA

42 SAFINAMIDE USFDA

43 SEMAGLUTIDE    USFDA+EMA

43A SODIUM ZIRCONIUM CYCLOCYLICATE        EMA

44 SOFOSBUVIR    USFDA+EMA

44A SPHEROX       EMA

45 TELOTRISTAT ETHYL    USFDA+EMA

45A TIVOZANIB        EMA

45B TOFACITINIB      EMA

45C TRUMENBA        EMA

46 VABORBACTAM USFDA

47 VALBENAZINE  USFDA

48 VESTRONIDASE ALFA-VJBK USFDA

49 VELPATASVIR    USFDA+EMA

50 VOXILAPREVIR     USFDA+EMA

Drugs EMA list missed out in usfda list

3A ALOFISEL

link………https://newdrugapprovals.org/2018/03/02/alofisel-darvadstrocel-cx-601/

4A Atezolizumab

WILL BE UPDATED

10A BUROSUMAB

WILL BE UPDATED

10B CARIPRAZINE HYDROCHLORIDE

WILL BE UPDATED

22B FLUCICLOVINE

Image result for FLUCICLOVINE

LINK https://newdrugapprovals.org/2016/05/28/fda-approves-new-diagnostic-imaging-agent-fluciclovine-f-18-to-detect-recurrent-prostate-cancer/

SEE EMA

Axumin : EPAR – Summary for the public EN = English 06/07/2017

http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/004197/human_med_002100.jsp&mid=WC0b01ac058001d124

Marketing-authorisation holder Blue Earth Diagnostics Ltd
Revision 0
Date of issue of marketing authorisation valid throughout the European Union 22/05/2017

Contact address:

Blue Earth Diagnostics Ltd
215 Euston Road
London NW1 2BE
United Kingdom

27A Lutetium lu 177 dotatate

WILL BE UPDATED

34A NONACOG

WILL BE UPDATED

34B NUCINERSEN

EMA AND JAPAN 2017 APPROVED

Nusinersen sodium colored.svg

Image result for Nusinersen sodium

LINK …….https://newdrugapprovals.org/2018/03/14/nusinersen-sodium-%E3%83%8C%E3%82%B7%E3%83%8D%E3%83%AB%E3%82%BB%E3%83%B3%E3%83%8A%E3%83%88%E3%83%AA%E3%82%A6%E3%83%A0/

35A OXERVATE

WILL BE UPDATED

36A PATIROMER

WILL BE UPDATED

36B PADELIPORFIN

img

NAME Tookad
AGENCY PRODUCT NUMBER EMEA/H/C/004182
ACTIVE SUBSTANCE padeliporfin di-potassium
INTERNATIONAL NON-PROPRIETARY NAME(INN) OR COMMON NAME padeliporfin
THERAPEUTIC AREA Prostatic Neoplasms
ANATOMICAL THERAPEUTIC CHEMICAL (ATC) CODE L01XD07
ADDITIONAL MONITORING This medicine is under additional monitoring. This means that it is being monitored even more intensively than other medicines. For more information, see medicines under additional monitoring.
MARKETING-AUTHORISATION HOLDER STEBA Biotech S.A
REVISION 0
DATE OF ISSUE OF MARKETING AUTHORISATION VALID THROUGHOUT THE EUROPEAN UNION 10/11/2017

Contact address:

STEBA Biotech S.A
7 place du theatre
L-2613 Luxembourg
Luxembourg

Image result for PADELIPORFIN

38A PRALATREXATE 

Pralatrexate.png

Japan approved 2017

2017/7/3 PMDA JAPAN Pralatrexate Difolta Mundipharma NME

LINK https://newdrugapprovals.org/2018/03/16/pralatrexate-%E3%83%97%E3%83%A9%E3%83%A9%E3%83%88%E3%83%AC%E3%82%AD%E3%82%B5%E3%83%BC%E3%83%88/

39A ROLAPITANT

WILL BE UPDATED

39B RURLOCTOCOG

WILL BE UPDATED

 43A SODIUM ZIRCONIUM

WILL BE UPDATED

 44A SPHEROX

WILL BE UPDATED

45A TIVOZANIB

Image result for TIVOZANIB EMAImage result for TIVOZANIB EMA

Pharmacotherapeutic group

Antineoplastic agents

Therapeutic indication

Fotivda is indicated for the first line treatment of adult patients with advanced renal cell carcinoma (RCC) and for adult patients who are VEGFR and mTOR pathway inhibitor-naïve following disease progression after one prior treatment with cytokine therapy for advanced RCC.

Treatment of advanced renal cell carcinoma

Fotivda : EPAR -Product Information

http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/004131/human_med_002146.jsp&mid=WC0b01ac058001d124

http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Public_assessment_report/human/004131/WC500239035.pdf

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Tivozanib is synthesized in three main steps using well defined starting materials with acceptable
specifications.
Adequate in-process controls are applied during the synthesis. The specifications and control methods for
intermediate products, starting materials and reagents have been presented. The critical process
parameters are duly justified, methodology is presented and control is adequate.
The characterisation of the active substance and its impurities are in accordance with the EU guideline on
chemistry of new active substances. Potential and actual impurities were well discussed with regards to
their origin and characterised.
The active substance is packaged in a low-density polyethylene (LDPE) bag which complies with the EC
directive 2002/72/EC and EC 10/2011 as amended.

Product details

Name Fotivda
Agency product number EMEA/H/C/004131
Active substance tivozanib
International non-proprietary name(INN) or common name tivozanib hydrochloride monohydrate
Therapeutic area Carcinoma, Renal Cell
Anatomical therapeutic chemical (ATC) code L01XE

Publication details

Marketing-authorisation holder EUSA Pharma (UK) Limited
Revision 0
Date of issue of marketing authorisation valid throughout the European Union 24/08/2017

Contact address:

EUSA Pharma (UK) Limited
Breakspear Park, Breakspear Way
Hemel Hempstead, HP2 4TZ
United Kingdom

LINK………https://newdrugapprovals.org/2018/02/26/tivozanib-%E3%83%86%E3%82%A3%E3%83%9C%E3%82%B6%E3%83%8B%E3%83%96%E5%A1%A9%E9%85%B8%E5%A1%A9%E6%B0%B4%E5%92%8C%E7%89%A9/

45B TOFACITINIB

WILL BE UPDATED

45C TRUMENBA

WILL BE UPDATED

SECTION C JAPANFORODOS

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SECTION C  New Drugs JAPAN

https://www.pmda.go.jp/english/review-services/reviews/approved-information/drugs/0002.html

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JAPAN 2017

2017/9/27 Avelumab (genetical recombination) Bavencio Merck Serono BLA
2017/9/27 Glecaprevir – pibrentasvir mixt Maviret Abbvie NME
2017/9/27 Daratumumab (genetical recombination) Darzalex Janssen Pharmaceutical BLA
2017/9/27 Belimumab (genetical recombination) Benlysta GlaxoSmithKline BLA
2017/9/27 Bezlotoxumab (genetical recombination) Zinplava MDS BLA
2017/9/27 Palbociclib Ibrance Pfizer NME
2017/9/27 Lonoctocog alfa (genetical recombination) Afstyla CSL Behring BLA
2017/9/27 Rupatadine fumarate Rupafin Teikoku seiyaku NME
2017/9/27 Sarilumab (genetical receombination) Kevzara Sanofi BLA
2017/9/27 Flutemetamol (18F) Vizamyl Nihon Medi-Physics NME
2017/7/3 Nusinersen sodium Spinraza Biogen Japan
2017/7/3 Romidepsin Istodax Celgene NME
2017/7/3 Pralatrexate Difolta Mundipharma NME
2017/7/3 Amenamevir Amenalief Maruho NME
2017/7/3 Baricitinib Olumiant Lilly NME
2017/7/3 Pemafibrate Parmodia Kowa NME
2017/3/30 Human prothrombin complex, freeze-dried concentrated Kcentra CSL Behring
2017/3/30 Ixazomib citrate Ninlaro Takeda NME
2017/3/30 Forodesine hydrochloride Mundesine Mundipharma
2017/3/30 Aflibercept beta (genetical recombination) Zaltrap Sanofi
2017/3/30 Hydromorphone hydrochloride Narusus, Narurapid DaiichiSankyo-pp
2017/3/30 Naldemedine tosylate Symproic Shionogi NME
2017/3/30 Guanfacine hydrochloride Intuniv Shionogi

3B AMENAMEVIR

Originally developed by Astellas, the drug was licensed to Maruho. Amenamevir treats herpes zoster by inhibiting the activity of the helicase-primer enzyme during viral DNA replication and blocking the virus’s proliferation.

Amenalief® is an oral film-coated tablet containing 200 mg of amenamevir per tablet. Recommended dose of 1 day, 400mg each time, after meals.

LINK https://newdrugapprovals.org/2018/03/12/amenamevir-%E3%82%A2%E3%83%A1%E3%83%8A%E3%83%A1%E3%83%93%E3%83%AB/

22A FORODESINE HYDROCHLORIDE

LINK  https://newdrugapprovals.org/2018/03/06/forodesine-hydrochloride/

6A BARICITINIB   JAPAN

Originally developed by Incyte, Baricitinib was later licensed to and for sale by Lilly under the trade name Olumiant®. Baricitinib is an irreversible inhibitor of Janus kinase 1 (JAK1) and Janus kinase 2 (JAK2). Olumiant® is approved for the treatment of mild to moderate rheumatoid arthritis in adult patients who are not responsive or intolerant to other anti-arthritic drugs. This product can be used alone or in combination with methotrexate.

Olumiant® is a film-coated tablet containing 2 mg or 4 mg per tablet. Recommended oral dose is 4mg daily, with meals or fasting food, you can take any time period.

2017/7/3PMDA   Baricitinib Olumiant Lilly

LINK https://newdrugapprovals.org/2013/06/17/lilly-and-partner-incyte-corp-have-presented-more-promising-data-on-their-investigational-jak-inhibitor-baricitinib-for-rheumatoid-arthritis/

36C PEMAFIBRATE 

LINK   https://newdrugapprovals.org/2016/04/24/pemafibrate/

SECTION D

CDSCO INDIA


http://www.cdsco.nic.in/forms/list.aspx?lid=2034&Id=11 http://www.cdsco.nic.in/forms/list.aspx?lid=2034&Id=11

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KEEP WATCHING UNDER CONSTRUCTION AND WILL BE PASTED SOON………………………………………..

KEEP WATCHING UNDER CONSTRUCTION AND WILL BE PASTED SOON………………………………………..

KEEP WATCHING UNDER CONSTRUCTION AND WILL BE PASTED SOON………………………………………..

KEEP WATCHING UNDER CONSTRUCTION AND WILL BE PASTED SOON………………………………………..

REFERENCES

http://www.ema.europa.eu/ema/index.jsp?curl=pages/news_and_events/news/2018/01/news_detail_002886.jsp&mid=WC0b01ac058004d5c1

http://www.ema.europa.eu/docs/en_GB/document_library/Report/2018/01/WC500242079.pdf

“NEW DRUG APPROVALS” CATERS TO EDUCATION GLOBALLY, No commercial exploits are done or advertisements added by me. This is a compilation for educational purposes only. P.S. : The views expressed are my personal and in no-way suggest the views of the professional body or the company that I represent

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Anthony Melvin Crasto Dr.

amcrasto@gmail.com

I , Dr A.M.Crasto is writing this blog to share the knowledge/views, after reading Scientific Journals/Articles/News Articles/Wikipedia. My views/comments are based on the results /conclusions by the authors(researchers). I do mention either the link or reference of the article(s) in my blog and hope those interested can read for details. I am briefly summarising the remarks or conclusions of the authors (researchers). If one believe that their intellectual property right /copyright is infringed by any content on this blog, please contact or leave message at below email address amcrasto@gmail.com. It will be removed ASAP

////////EMA APPROVALS, USFDA Approvals, ACALABRUTINIBAVELUMABBETRIXABANBRODALUMABCOPANLISIBDEFLAZACORTDelafloxacinDeutetrabenazineDUPILUMABETELCALCETIDENaldemedineNETARSUDILNIRAPARIBOcrelizumabPLECANATIDERIBOCICLIBSAFINAMIDETELOTRISTAT ETHYL, VALBENAZINE, CERLIPONASE, BRIGATINIB, MIDOSTAURIN, Abaloparatide, BENZNIDAZOLENERATINIBinotuzumab ozogamicinEnasidenib, LETERMOVIR, GLECAPREVIR, PIBRENTASVIR, VOXILAPREVIR, SOFOSBUVIR, EDAVARONE, abemaciclib, ANGIOTENSIN II, VESTRONIDASE, macimorelin acetate, ERTUGLIFLOZIN, SEMAGLUTIDE, EMICIZUMAB, eu 2017, fda 2017, BENRALIZUMAB, DURVALUMAB, GUSELKUMAB, LATANOPROSTENE, OZENOXACIN, SARILUMAB, SECNIDAZOLE, BENRALIZUMAB, TIVOZANIB, SARILUMAB, FLUCICLOVINE, 

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