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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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FDA approves Odactra for house dust mite allergies


Image result for fda approved
03/01/2017
The U.S. Food and Drug Administration today approved Odactra, the first allergen extract to be administered under the tongue (sublingually) to treat house dust mite (HDM)-induced nasal inflammation (allergic rhinitis), with or without eye inflammation (conjunctivitis), in people 18 through 65 years of age.

March 1, 2017

Release

The U.S. Food and Drug Administration today approved Odactra, the first allergen extract to be administered under the tongue (sublingually) to treat house dust mite (HDM)-induced nasal inflammation (allergic rhinitis), with or without eye inflammation (conjunctivitis), in people 18 through 65 years of age.

“House dust mite allergic disease can negatively impact a person’s quality of life,” said Peter Marks, M.D., Ph.D., director of the FDA’s Center for Biologics Evaluation and Research. “The approval of Odactra provides patients an alternative treatment to allergy shots to help address their symptoms.”

House dust mite allergies are a reaction to tiny bugs that are commonly found in house dust. Dust mites, close relatives of ticks and spiders, are too small to be seen without a microscope. They are found in bedding, upholstered furniture and carpeting. Individuals with house dust mite allergies may experience a cough, runny nose, nasal itching, nasal congestion, sneezing, and itchy and watery eyes.

Odactra exposes patients to house dust mite allergens, gradually training the immune system in order to reduce the frequency and severity of nasal and eye allergy symptoms. It is a once-daily tablet, taken year round, that rapidly dissolves after it is placed under the tongue. The first dose is taken under the supervision of a health care professional with experience in the diagnosis and treatment of allergic diseases. The patient is to be observed for at least 30 minutes for potential adverse reactions. Provided the first dose is well tolerated, patients can then take Odactra at home. It can take about eight to 14 weeks of daily dosing after initiation of Odactra for the patient to begin to experience a noticeable benefit.

The safety and efficacy of Odactra was evaluated in studies conducted in the United States, Canada and Europe, involving approximately 2,500 people. Some participants received Odactra, while others received a placebo pill. Participants reported their symptoms and the need to use symptom-relieving allergy medications. During treatment, participants taking Odactra experienced a 16 to 18 percent reduction in symptoms and the need for additional medications compared to those who received a placebo.

The most commonly reported adverse reactions were nausea, itching in the ears and mouth, and swelling of the lips and tongue. The prescribing information includes a boxed warning that severe allergic reactions, some of which can be life-threatening, can occur. As with other FDA-approved allergen extracts administered sublingually, patients receiving Odactra should be prescribed auto-injectable epinephrine. Odactra also has a Medication Guide for distribution to the patient.

Odactra is manufactured for Merck, Sharp & Dohme Corp., (a subsidiary of Merck and Co., Inc., Whitehouse Station, N.J.) by Catalent Pharma Solutions Limited, United Kingdom.

(sublingually) to treat house dust mite (HDM)-induced nasal inflammation (allergic rhinitis), with or without eye inflammation (conjunctivitis), in people 18 through 65 years of age

/////////////Odactra,  Merck, Sharp & Dohme Corp,  Catalent Pharma Solutions Limited, United Kingdom, FDA 2017, approves,  house dust mite allergies

FDA approves Intrarosa for postmenopausal women experiencing pain during sex


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FDA approves Intrarosa for postmenopausal women experiencing pain during sex

The U.S. Food and Drug Administration approved Intrarosa (prasterone) to treat women experiencing moderate to severe pain during sexual intercourse (dyspareunia), a symptom of vulvar and vaginal atrophy (VVA), due to menopause. Intrarosa is the first FDA approved product containing the active ingredient prasterone, which is also known as dehydroepiandrosterone (DHEA).

Read more

http://www.fda.gov/newsevents/newsroom/pressannouncements/UCM529641.htm?source=govdelivery&utm_medium=email&utm_source=govdelivery

For Immediate Release

November 17, 2016

Release

The U.S. Food and Drug Administration approved Intrarosa (prasterone) to treat women experiencing moderate to severe pain during sexual intercourse (dyspareunia), a symptom of vulvar and vaginal atrophy (VVA), due to menopause. Intrarosa is the first FDA approved product containing the active ingredient prasterone, which is also known as dehydroepiandrosterone (DHEA).

During menopause, levels of estrogen decline in vaginal tissues, which may cause a condition known as VVA, leading to symptoms such as pain during sexual intercourse.

“Pain during sexual intercourse is one of the most frequent symptoms of VVA reported by postmenopausal women,” said Audrey Gassman, M.D., deputy director of the Division of Bone, Reproductive, and Urologic Products (DBRUP) in the Office of Drug Evaluation III in the FDA’s Center for Drug Evaluation and Research (CDER). “Intrarosa provides an additional treatment option for women seeking relief of dyspareunia caused by VVA.”

Efficacy of Intrarosa, a once-daily vaginal insert, was established in two 12-week placebo-controlled clinical trials of 406 healthy postmenopausal women, 40 to 80 years of age, who identified moderate to severe pain during sexual intercourse as their most bothersome symptom of VVA. Women were randomly assigned to receive Intrarosa or a placebo vaginal insert. Intrarosa, when compared to placebo, was shown to reduce the severity of pain experienced during sexual intercourse.

The safety of Intrarosa was established in four 12-week placebo-controlled trials and one 52-week open-label trial. The most common adverse reactions were vaginal discharge and abnormal Pap smear.

Although DHEA is included in some dietary supplements, the efficacy and safety of those products have not been established for diagnosing, curing, mitigating, treating or preventing any disease.

Intrarosa is marketed by Quebec-based Endoceutics Inc.

The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.

Dehydroepiandrosterone
Dehydroepiandrosteron.svg
Dehidroepiandrosterona3D.png
Systematic (IUPAC) name
(3S,8R,9S,10R,13S,14S)-3-hydroxy-10,13-dimethyl-1,2,3,4,7,8,9,11,12,14,15,16-dodecahydrocyclopenta[a]phenanthren-17-one; (1S,2R,5S,10R,11S,15S)-5-Hydroxy-2,15-dimethyltetracyclo[8.7.0.02,7.011,15]heptadec-7-en-14-one
Clinical data
Routes of
administration
Oral
Legal status
Legal status
Pharmacokinetic data
Metabolism Hepatic
Biological half-life 12 hours
Excretion Urinary:?%
Identifiers
CAS Number 53-43-0 Yes
ATC code A14AA07 (WHO)
G03EA03 (WHO) (combination with estrogen)
PubChem CID 5881
IUPHAR/BPS 2370
DrugBank DB01708 Yes
ChemSpider 5670 Yes
UNII 459AG36T1B Yes
ChEBI CHEBI:28689 Yes
ChEMBL CHEMBL90593 Yes
Synonyms (3β)-3-Hydroxyandrost-5-en-17-one
Chemical data
Formula C19H28O2
Molar mass 288.424 g/mol
3D model (Jmol) Interactive image
 //////////////////
 FDA,  approves,  Intrarosa, postmenopausal women, pain during sex, prasterone, dehydroepiandrosterone,  (DHEA).

Page Last Updated: 11/17/2016
Note: If you need help accessing information in different file formats, see Ins

USFDA approves Indoco’s Allopurinol ANDA


usfda-approval-Allopurinol-forprint.jpg

Indoco Remedies Limited (India) | Facebook

https://www.facebook.com/Indoco-Remedies-Limited-India-317944458228011/

USFDA approves Indoco’s Allopurinol ANDA… Indoco Remedies Limited (India)’s … Indoco Remedies Limited (India) added a new photo

Allopurinol 3d structure.png

Allopurinol, sold under the brand name Zyloprim and generics, is a medication used primarily to treat excess uric acid in the bloodand its complications, including chronic gout. It is a xanthine oxidase inhibitor and is administered orally.

It is on the World Health Organization’s List of Essential Medicines, a list of the most important medication needed in a basic health system.

Allopurinol has been marketed in the United States since August 19, 1966, when it was first approved by FDA under the trade name Zyloprim. Allopurinol was marketed at the time by Burroughs-Wellcome. Allopurinol is now a generic drug sold under a variety of brand names, including Allohexal, Allosig, Milurit, Alloril, Progout, Ürikoliz, Zyloprim, Zyloric, Zyrik, and Aluron

Aditi Kare Panandikar, Managing Director, Indoco Remedies

click above

Aditi Kare Panandikar gets award

///////////Indoco Remedies LtdUSFDA,  approves,  Indoco’s,  Allopurinol,  ANDA, Aditi Kare Panandikar, Managing Director,

FDA approves Adlyxin (lixisenatide) 利西拉 to treat type 2 diabetes


 

 

07/28/2016 07:53 AM EDT
The U.S. Food and Drug Administration approved Adlyxin (lixisenatide), a once-daily injection to improve glycemic control (blood sugar levels), along with diet and exercise, in adults with type 2 diabetes.

July 28, 2016

Release

The U.S. Food and Drug Administration approved Adlyxin (lixisenatide), a once-daily injection to improve glycemic control (blood sugar levels), along with diet and exercise, in adults with type 2 diabetes.

“The FDA continues to support the development of new drug therapies for diabetes management,” said Mary Thanh Hai Parks, M.D., deputy director, Office of Drug Evaluation II in the FDA’s Center for Drug Evaluation and Research. “Adlyxin will add to the available treatment options to control blood sugar levels for those with type 2.”

Type 2 diabetes affects more than 29 million people and accounts for more than 90 percent of diabetes cases diagnosed in the United States. Over time, high blood sugar levels can increase the risk for serious complications, including heart disease, blindness and nerve and kidney damage.

Adlyxin is a glucagon-like peptide-1 (GLP-1) receptor agonist, a hormone that helps normalize blood sugar levels. The drug’s safety and effectiveness were evaluated in 10 clinical trials that enrolled 5,400 patients with type 2 diabetes. In these trials, Adlyxin was evaluated both as a standalone therapy and in combination with other FDA-approved diabetic medications, including metformin, sulfonylureas, pioglitazone and basal insulin. Use of Adlyxin improved hemoglobin A1c levels (a measure of blood sugar levels) in these trials.

In addition, more than 6,000 patients with type 2 diabetes at risk for atherosclerotic cardiovascular disease were treated with either Adlyxin or a placebo in a cardiovascular outcomes trial. Use of Adlyxin did not increase the risk of cardiovascular adverse events in these patients.

Adlyxin should not be used to treat people with type 1 diabetes or patients with increased ketones in their blood or urine (diabetic ketoacidosis).

The most common side effects associated with Adlyxin are nausea, vomiting, headache, diarrhea and dizziness. Hypoglycemia in patients treated with both Adlyxin and other antidiabetic drugs such as sulfonylurea and/or basal insulin is another common side effect. In addition, severe hypersensitivity reactions, including anaphylaxis, were reported in clinical trials of Adlyxin.

The FDA is requiring the following post-marketing studies for Adlyxin:

  • Clinical studies to evaluate dosing, efficacy and safety in pediatric patients.
  • A study evaluating the immunogenicity of lixisenatide.

Adlyxin is manufactured by Sanofi-Aventis U.S. LLC, of Bridgewater, New Jersey.

END……………….

 

 

lixisenatide;Lixisenatide|Lixisenatide Acetate;Lixisenatide Acetate
CAS: 320367-13-3
MF: C215H347N61O65S
MW: 4858.53

C215 H347 N61 O65 S

L-Lysinamide, L-histidylglycyl-L-α-glutamylglycyl-L-threonyl-L-phenylalanyl-L-threonyl-L-seryl-L-α-aspartyl-L-leucyl-L-seryl-L-lysyl-L-glutaminyl-L-methionyl-L-α-glutamyl-L-α-glutamyl-L-α-glutamyl-L-alanyl-L-valyl-L-arginyl-L-leucyl-L-phenylalanyl-L-isoleucyl-L-α-glutamyl-L-tryptophyl-L-leucyl-L-lysyl-L-asparaginylglycylglycyl-L-prolyl-L-seryl-L-serylglycyl-L-alanyl-L-prolyl-L-prolyl-L-seryl-L-lysyl-L-lysyl-L-lysyl-L-lysyl-L-lysyl-

L-Histidylglycyl-L-α-glutamylglycyl-L-threonyl-L-phenylalanyl-L-threonyl-L-seryl-L-α-aspartyl-L-leucyl-L-seryl-L-lysyl-L-glutaminyl-L-methionyl-L-α-glutamyl-L-α-glutamyl-L-α-glutamyl-L-alanyl-L-valyl-L-arginyl-L-leucyl-L-phenylalanyl-L-isoleucyl-L-α-glutamyl-L-tryptophyl-L-leucyl-L-lysyl-L-asparaginylglycylglycyl-L-prolyl-L-seryl-L-serylglycyl-L-alanyl-L-prolyl-L-prolyl-L-seryl-L-lysyl-L-lysyl-L-lysyl-L-lysyl-L-lysyl-L-lysinamide

 

827033-10-3.png

Lixisenatide

Lixisenatide

 

827033-10-3; Lixisenatide [INN]; UNII-74O62BB01U; DesPro36Exendin-4(1-39)-Lys6-NH2;   DesPro36Exendin-4(1-39)-Lys6-NH2
Molecular Formula: C215H347N61O65S
Molecular Weight: 4858.49038 g/mol
IUPAC Condensed

H-His-Gly-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Leu-Ser-Lys-Gln-Met-Glu-Glu-Glu-Ala-Val-Arg-Leu-Phe-Ile-Glu-Trp-Leu-Lys-Asn-Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Ser-Lys-Lys-Lys-Lys-Lys-Lys-NH2

from PubChem
LINUCS

[][L-Lys-NH2]{[(1+2)][L-Lys]{[(1+2)][L-Lys]{[(1+2)][L-Lys]{[(1+2)][L-Lys]{[(1+2)][L-Lys]{[(1+2)][L-Ser]{[(1+2)][L-Pro]{[(1+2)][L-Pro]{[(1+2)][L-Ala]{[(1+2)][Gly]{[(1+2)][L-Ser]{[(1+2)][L-Ser]{[(1+2)][L-Pro]{[(1+2)][Gly]{[(1+2)][Gly]{[(1+2)][L-Asn]{[(1+2)][L-Lys]{[(1+2)][L-Leu]{[(1+2)][L-Trp]{[(1+2)][L-Glu]{[(1+2)][L-Ile]{[(1+2)][L-Phe]{[(1+2)][L-Leu]{[(1+2)][L-Arg]{[(1+2)][L-Val]{[(1+2)][L-Ala]{[(1+2)][L-Glu]{[(1+2)][L-Glu]{[(1+2)][L-Glu]{[(1+2)][L-Met]{[(1+2)][L-Gln]{[(1+2)][L-Lys]{[(1+2)][L-Ser]{[(1+2)][L-Leu]{[(1+2)][L-Asp]{[(1+2)][L-Ser]{[(1+2)][L-Thr]{[(1+2)][L-Phe]{[(1+2)][L-Thr]{[(1+2)][Gly]{[(1+2)][L-Glu]{[(1+2)][Gly]{[(1+2)][L-His]{}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}

from PubChem
Sequence

HGEGTFTSDLSKQMEEEAVRLFIEWLKNGGPSSGAPPSKKKKKK

from PubChem
PLN

H-HGEGTFTSDLSKQMEEEAVRLFIEWLKNGGPSSGAPPSKKKKKK-[NH2]

from PubChem
HELM

PEPTIDE1{H.G.E.G.T.F.T.S.D.L.S.K.Q.M.E.E.E.A.V.R.L.F.I.E.W.L.K.N.G.G.P.S.S.G.A.P.P.S.K.K.K.K.K.K.[am]}$$$$

Sanofi (formerly sanofi-aventis, formerly Aventis), under license from Zealand Pharma, has developed and launched lixisenatide

Lixisenatide (trade name Lyxumia) is a once-daily injectable GLP-1 receptor agonist for the treatment of diabetes, discovered by Zealand Pharma A/S of Denmark and licensed and developed by Sanofi.[1] Lixisenatide was accepted for review by the US FDA on February 19, 2013, and approved by the European Commission on February 1, 2013.[2] On September 12, 2013, Sanofi delayed the approval process in the US, citing internal data from a cardiovascular risk study. The drug will likely be resubmitted for approval in 2015.

Lixisenatide is a once-daily injectable GLP-1 receptor agonist discovered by Zealand Pharma A/S of Denmark and licensed and developed by Sanofi. As of September 2010 it is in clinical trials for diabetes. Lixisenatide was accepted for review by the US FDA on February 19, 2013, and approved by the European Commission on February 1, 2013. The drug will likely be resubmitted for approval in 2015.

Mechanism of action

GLP-1 is a naturally-occurring peptide that is released within minutes of eating a meal. It is known to suppress glucagon secretion from pancreatic alpha cells and stimulate insulin secretion by pancreatic beta cells. GLP-1 receptor agonists are used as an add-on treatment for type 2 diabetes and their use is endorsed by the European Association for the Study of Diabetes, the American Diabetes Association, the American Association of Clinical Endocrinologists and the American College of Endocrinology.

Physical and chemical properties

Lixisenatixe has been described as “des-38-proline-exendin-4 (Heloderma suspectum)-(1–39)-peptidylpenta-L-lysyl-L-lysinamide”, meaning it is derived from the first 39 amino acids in the sequence of the peptide exendin-4, found in the Gila monster (Heloderma suspectum), omitting proline at position 38 and adding six lysine residues. Its complete sequence is:[3]

H–HisGlyGlu–Gly–ThrPhe–Thr–SerAspLeu–Ser–LysGlnMet–Glu–Glu–Glu–AlaValArg–Leu–Phe–Ile–Glu–Trp–Leu–Lys–Asn–Gly–Gly–Pro–Ser–Ser–Gly–Ala–Pro–Pro–Ser–Lys–Lys–Lys–Lys–Lys–Lys–NH2

PATENT

US 20110313131

http://www.google.co.in/patents/US20110313131

 

PATENT

CN 105713082

The title method comprises the steps of: (1) coupling Fmoc-Lys(Boc)-OH and resin to obtain Fmoc-Lys(Boc)-resin, (2) protecting amino acid with Fmoc, conducting solid-phase synthesis to obtain lixisenatide wholly protected 20-44-peptide resin, (3) conducting solid-phase synthesis to obtain wholly protected 15-19-peptide resin, (4) coupling the wholly protected 20-44-peptide resin and wholly protected 15-19-peptide resin, (5) coupling other amino acids till solid-phase synthesis finishes, (6) cracking lixisenatide peptide resin to obtain crude peptide, and (7) purifying through RP-HPLC.  The method improves crude peptide purity and purifn. yield.

PATENT

CN104211801A

MACHINE TRANSLATION FROM CHINESE, PL BEAR WITH SOME IREGULARITES IN GRAMMAR

利西拉, the English name: Lixisenatide, is a polypeptide containing 44 amino acids, the structural formula is as follows: peptide sequence as follows:

Figure CN104211801AD00031

H-His-Gly-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Leu-Ser-Lys-Gln-Met-Glu-Glu-Glu-Al a-Val-Arg-Leu-Phe-IIe-Glu -Trp-Leu-Lys-Asn-Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pr O-Ser-Lys-Lys-Lys-Lys-Lys-Lys-NH 2 Li Xila to (Lixisenatide ) by Sanofi-Aventis developed once a day subcutaneously with glucagon-like peptide -I (GLP-I) receptor agonists, for the treatment of type II diabetes, on February 1, 2013 Sanofi Lee Division -Aventis of exenatide is approved EMEA, for the adjuvant treatment of poorly stable dose of basal insulin (or metformin) in the treatment of type II diabetes to improve HbAlc and postprandial blood glucose levels.

CN201210030151. 2 used in a pure solid phase sequential coupling method synthetic peptides. The method amino resin as the carrier, using conventional coupling sequence, the final cut to give Li Xila.

 US6528486 patent for the compound, synthetic methods mentioned it to phase condensation method Fmoc / tBu strategy.

The [0005] W02005058954 synthesis method including the gradual condensation process Fmoc / tBu strategy, Boc strategy of gradual condensation methods and genetic engineering.

The  W02001004156 synthesis method for the gradual condensation process Fmoc / tBu strategy.

 Since Li Xila abroad mostly used to synthesize Fmoc solid phase synthesis method, a gradual shrinking gradually synthesis step more, resulting in more types of product impurities, US 20130284912 Special Report polypeptide impurity: Di-Ser33- Leisy pull and Di-Ala35- Li Xila come, Di-Ser 33- Li Xila come and Di-Ala35- Li Xila to atmosphere amino acid sequence as follows: Di-Ser33- Li Xila to the amino acid sequence: H-His -Gly-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Leu-Ser-Lys-Gln-Met-Glu-Glu-Glu-Al a-Val-Arg-Leu-Phe-IIe-Glu-Trp- Leu-Lys-Asn-Gly-Gly-Pro-Ser-Ser-Ser-Gly-Ala-Pr 〇-Pr〇-Ser-Lys_Lys_Lys_Lys_Lys_LyS-NH2 Di-Ala35- Li Xila to the amino acid sequence: H-His-Gly- Glu-Gly-Thr-Phe-Thr-Ser-Asp-Leu-Ser-Lys-Gln-Met-Glu-Glu-Glu-Al a-Val-Arg-Leu-Phe-IIe-Glu-Trp-Leu-Lys -Asn-Gly-Gly-Pro-Ser-Ser-Gly-Ala-Ala-Pr 〇-Pr〇-Ser-Lys_Lys_Lys_Lys_Lys_LyS-NH2 toxicity of these impurities are impurities larger, and very difficult to separate from the main peak , the presence of the impurities seriously affect 利西拉 to content and the use of safety. Hence the need to find an effective way to remove it and to reach the high standard level of 0.1% or less. The present inventors have found that this impurity is difficult to remove by means of the prior art, although there are ways to remove part of, but removal is not ideal, it is difficult to achieve high quality standards is likely to cause 利西拉 level while reducing their yield.

In summary, the existing Li Xila to the solid phase synthesis, low yield of the synthesis, impurities, in particular, are not well controlled impurity Di-Ser 33- Li Xila come and Di-Ala35 – Li Xila to, does not apply to industrial production

Example i ^ a: Preparation 利西拉 to fine peptide acetate Weigh 利西拉 above 44. 70g to 45L crude peptide was dissolved in water, purified by C18 column, the first purification conditions: mobile phase: A phase: 0 I% TFA; B phase: acetonitrile; gradient program was: 15% B, 60 minutes to 60% B; detection wavelength 220 nm; peak fraction collection purposes. The second purification conditions: mobile phase was: A phase: 0 3% HAC; B phase: acetonitrile; gradient program was: 10% B, 60 minutes to 60% B; detection wavelength 220 nm; peak fraction collection purposes. Desalting conditions: Mobile phase: A phase: an aqueous solution of 20 mmol / L ammonium acetate: acetonitrile = 95: 5; B phase: water: acetonitrile = 95: 5; C phase: 0.03% aqueous solution of acetic acid: acetonitrile = 95 : 5; D phase: 0.03% aqueous solution of acetic acid: acetonitrile = 50: 50; gradient program: mobile phase A isocratic for 15 minutes, convert isocratic mobile phase B for 10 minutes, is converted into the flow Phase C isocratic 10 minutes, converted into a mobile phase D isocratic 25 minutes; detection wavelength 220 nm; peak fraction collection purposes; rotary evaporation concentrated and lyophilized to give Li Xila acetate fine peptide 22. 65g which HPLC spectrum shown in Figure 5, HPLC purity of 99.75% (area normalization method), Di-Ser33- Li Xila come to 0.03% (area normalization method), Di-Ala35- Li Xila to the content of 0.05% (area normalization method). Purification total yield of 51%, total yield 41%. Its mass spectrum as shown in Figure 6, [M + H] + = 4858. 691, 利西拉 precise molecular weight to the theoretical: 4857.53, the sample mass is consistent with the theoretical molecular weight.

PATENT

CN 103709243

MACHINE TRANSLATION FROM CHINESE, PL BEAR WITH SOME IREGULARITES IN GRAMMAR

Example 2: Preparation 利西拉 to crude peptide

利西拉 [0116] Example 24 was prepared to be placed 125.4g peptide resin cleavage reaction to 10ml / g resin ratio added lysis reagent (TFA: thioanisole: EDT: TIS: water = 86: 5 : 5: 3: 1 (V / V)), stirred at room temperature 2.5h. The reaction was purified by frit funnel filtration, the filtrate was collected, the resin was washed 3 times and then a small amount of TFA, the combined filtrates concentrated under reduced pressure. Frozen precipitation in anhydrous ether was added, washed three times with anhydrous diethyl ether, and dried in vacuo to give a white solid powder, i.e. Li Xila to crude peptide 47.lg, by weight of the crude peptide yield 97.2%, HPLC purity 63.8% 0

利西拉 to crude peptide preparation: 27 patients [0117] Example

利西拉 [0118] The Example 25 was prepared to be placed 123.7g peptide resin cleavage reaction to 10ml / g resin ratio added lysis reagent (TFA: thioanisole: EDT: TIS: water = 86: 5 : 5: 3: 1 (V / V)), stirred at room temperature 2.5h. The reaction was purified by frit funnel filtration, the filtrate was collected, the resin was washed 3 times and then a small amount of TFA, the combined filtrates concentrated under reduced pressure. Frozen precipitation in anhydrous ether was added, washed three times with anhydrous diethyl ether, and dried in vacuo to give a white solid powder, i.e. Li Xila to crude peptide 46.9g, yield the crude peptide by weight 96.5%, HPLC purity 64.2% 0

28 Example 2: Preparation 利西拉 to fine peptide acetate

 Example weighed 26 to 27 after 利西拉 to any 30.0g crude peptide was dissolved in 3000ml of water using Waters2545RP-HPLC system, wavelength 230nm, 50 X 250mm column of reverse phase C18 column, 0.2% TFA conventional / acetonitrile mobile phase were fractionated peaks of fractions, refined peptide purity greater than 98.5%. The fine peptide solution using Waters2545RP-HPLC system, 50 X 250mm column was C18 reverse phase column, 0.1% acetic acid / acetonitrile mobile phase transfer salt, the purpose of peak fractions were collected, concentrated by rotary evaporation and lyophilized to give Li Xila acetate fine salt peptide> 9.0g, RP-HPLC purity ≥98.5%. Purification Yield ≥30%, total yield ≥29.0%.

PATENT

CN 102875663

MACHINE TRANSLATION FROM CHINESE, PL BEAR WITH SOME IREGULARITES IN GRAMMAR

http://www.google.at/patents/CN102875663B?cl=en

Example 9

[0239] The crude peptide Li Xila to 4000g (including Li Xila to 1139g) was dissolved with purified water 100L, collected by filtration and the filtrate set aside.

[0240] purification chromatographic conditions:

[0241] HPLC Model: Novasep LC450

 Column: 450X250mm, built-phenyl silane bonded silica gel as stationary phase filler, the filler particle size of 10 μ m0

 flow rate: 5000ml / min.

The detection wavelength: 280nm.

 Mobile phase A phase: 10% 30mM D- 30mM sodium tartrate and disodium hydrogenphosphate in methanol / 90% aqueous (v / v), adjusted to pH 2.5 with phosphoric acid.

[0246] Mobile phase A phase preparation process: Weigh 1280g 2070g D- sodium tartrate and disodium hydrogenphosphate, after an appropriate amount of purified water was dissolved through 0.45 μ m membrane filter, the filtrate collected all 300L tank, added 30L chromatographically pure After methanol was added to the 300L scale purification of water, adjusted to pH 2.5 with phosphoric acid. Repeat preparation run.

[0247] The mobile phase B phase: HPLC grade acetonitrile.

Figure CN102875663BD00132

[0249] sample volume: 250.0g (6250ml).

[0250] Purification: column equilibration the sample so that after 5 minutes, run a gradient purification, monitoring and staging purposes peak fractions were collected. The collected fractions (chromatographic conditions purity testing to the same conditions as above 利西拉 determination to area normalization method measured) purity test, the purity of greater than or equal to 98% of the fractions after removing most of the acetonitrile in turn salt; purity of 70% or more less than 98% of the fraction recovered after removal of most of the acetonitrile and the purification procedure is repeated, again collected purity greater than or equal to 98% of the fraction after removal of most of the acetonitrile are also used to turn salt; purity of less than 70 % of fractions by waste disposal.

[0251] points and 16 injections, repeat the above operation.

[0252] turn salt chromatographic conditions:

[0253] HPLC Model: Novasep LC450

[0254] Column: 450 X 250mm, built-C8 reversed-phase chromatography packing, the particle size of the filler is 10 μ m.

[0255] flow rate: 5000ml / min.

[0256] The detection wavelength: 280nm.

[0257] Mobile phase A phase: 0.2% acetic acid (v / v) solution.

[0258] The mobile phase B phase: HPLC grade acetonitrile.

[0259] gradient

Figure CN102875663BD00141

[0260] sample volume: 2500ml.

[0261] Purification: The column equilibration the sample for 5 minutes, run a gradient purification, monitoring and collecting the target peak fractions. The purpose of the peak fractions were concentrated by rotary evaporation under reduced pressure to 9000ml after lyophilization.

[0262] After the freeze-dried to give a white powder refined peptide 704g. Purity of 98.39%, the impurity content of less than 0.5%. Purification yield 61.8% (in crude Li Xila to content), total yield of 17.6%.

PATENT

CN 102558338

MACHINE TRANSLATION FROM CHINESE, PL BEAR WITH SOME IREGULARITES IN GRAMMAR

Preparation of Fmoc-Lys (Boc) -Lys (Boc) -Lys (Boc) -Lys (Boc) -Rink Amide-MBHAResin:

[0096] To the resulting Fmoc-Lys (Boc) -Lys (Boc) -Lys (Boc) -RinkAmide-MBHAResin mouth of a 20% strength piperidine / DMF solution for 10 minutes, the reaction was drained, washed with DMF Resin 6 (50ml * 6). Weigh Fmoc-Lys (Boc) -〇H3.52g, H0Bt1.01g, HBTU2.84g, TMP1.98ml, DMF50ml added to dissolve slowly with stirring under ice-cooling for 3 minutes, at room temperature for 2 hours, the reaction Ninhydrin detection method completed, pumping off the reaction solution, DMF the resin was washed twice (50mlX2), DCM the resin was washed twice (50mlX2), to give Fmoc-Lys (B oc) -Lys (Boc) -Lys (Boc) -Lys (Boc) -RinkAmide-MBHAResin. As used in the above operation Fmoc-Lys (Boc) -OH: HOBt: HBTU: TMP ratio is 1: 1: 1: 2, wherein Fmoc-Lys (Boc) -OH is the number of moles of Fmoc-RinkAmide-MBHAResin number of moles 3 times.

[0097] Li Xila fully protected side chain was prepared to -Rink Amide-MBHA Resin:

[0098] To the resulting Fmoc-Lys (Boc) -Lys (Boc) -Lys (Boc) -Lys (Boc) -RinkAmide-MBHA Resin added 20% piperidine / DMF solution for 10 minutes, drained reaction solution, washed 6 times with DMF. Weigh Jie 111〇 (3-1 ^ 8 billion (3) -0 13.528, 1 (»Shu 1.018,01 (:!! 1.391111 added 50,111,101 ^ dissolve slowly stirring for 3 minutes in an ice bath, poured into the solid phase resin is mixed with the reaction column, at room temperature for 2 hours, the reaction Ninhydrin detection method is completed, the reaction solution was deprived, DMF the resin was washed twice (50ml X 2), DCM the resin was washed twice (50ml X 2), to give Fmoc-Lys ( Boc) -Lys (Boc) -Lys (Boc) -Lys (Boc) -Lys (Boc) -Rink Amide-MBHAResin above operation used by the Fmoc-Lys (Boc) -〇H:. HOBt: DIC ratio is 1: 1: L2, which Fmoc-Lys (Boc) is three times the number of moles -〇H Fmoc-Rink Amide-MBHA Resin moles of repeat after the coupling step, followed by the completion of the 39 lysine to first. connecting protected amino acids histidine, followed by addition of 20% piperidine / DMF solution for 10 minutes, the reaction was drained, DMF the resin was washed six times (50ml X 6), DCM the resin was washed six times (50ml X 6 ), MeOH contraction of the resin three times with MeOH 50ml, each contraction 5min. After the resin was dried in vacuo to give a full side-chain protected peptide resin to the Li Xila 27. 5g, weight resin 17. 5g.

[0099] Li Xila to crude peptide preparation:

[0100] Weigh side chains fully protected Li Xila to -Rink Amide-MBHA Resin 27. 5 grams, into a round bottom flask.Configuration 275 ml lysis buffer, wherein trifluoroacetic acid: thioanisole: ethanedithiol: anisole, phenol = 93: 4: 1: 1.5: 2 (volume ratio). Lysate in the refrigerator after the pre-freeze 1 hour before Sheng Youli put to Silas to -Rink Amide-MBHA Resin round bottom flask, stirred at room temperature for 2 hours. The reaction mixture was filtered, the resin was washed with 20ml TFA and the combined filtrate.

[0101] The volume of the filtrate was slowly poured into 2,750 ml of diethyl ether frozen (frozen advance ether), a white precipitate appears, at 3000 rpm / centrifuged 5 minutes, the resulting solid was washed twice with ether, then the solid was dried under vacuum to give Li Xila trifluoroacetate crude peptide to 15. 3g.

[0102] Li Xila to large scale production of fine peptide:

[0103] Sample Preparation: The crude peptide was dissolved in water, the sample was completely dissolved by membrane filtration, the filtrate was collected for use.

[0104] Purification conditions: Column: octadecyl silane bonded silica gel as stationary phase column, the column diameter and length: 300_X250mm. Mobile phase: A phase: 35mm〇l / L phosphoric acid solution adjusted with triethylamine to pH 6. 7; B phase: acetonitrile, flow rate: 2200ml / min, Gradient: B%: 12% ~32%, detection wavelength: 280nm . The injection volume was 75g. Purification process: the column with 50% acetonitrile rinse clean after balance sample, sample amount is 75g. Linear gradient 120min, the purpose of collecting peaks will be collected 利西拉 solution was concentrated by rotary evaporation under reduced pressure to about 80mg / ml and reserve the water temperature exceeds 40 ° C without conditions.

[0105] turn salt: turn salt conditions: Column: octadecyl silane bonded silica gel as stationary phase column, the column diameter and length: 300mmX250mm. Mobile phase: A phase: mass concentration of 0.2% aqueous acetic acid; B phase: HPLC grade acetonitrile, flow rate: 2200ml / min, detection wavelength: 280nm. Gradient: B%: 6% ~36%. The injection volume was 48-60g. Salt transfer process: the column with 50% acetonitrile rinse clean after the sample, the sample volume is 1600ml sample solution. Linear gradient 90min, the purpose of collecting peaks collected Li Xila to solutions were concentrated by rotary evaporation to about 80ml / g after go to the appropriate size vials, then freeze-dried to obtain the purity of greater than 99.5% The Li Xila come.

Old post

https://newdrugapprovals.org/2013/09/13/sanofi-to-withdraw-the-lixisenatide-new-drug-application-nda-in-the-u-s-the-company-plans-to-resubmit-the-nda-in-2015-after-completion-of-the-elixa-cv-study/

lixisenatide

Sanofi Provides Update on Lixisenatide New Drug Application in U.S.

Paris, France – September 12, 2013 – Sanofi (EURONEXT: SAN and NYSE: SNY) announced today its decision to withdraw the lixisenatide New Drug Application (NDA) in the U.S., which included early interim results from the ongoing ELIXA cardiovascular (CV) outcomes study. The company plans to resubmit the NDA in 2015, after completion of the ELIXA CV study.

The decision to withdraw the lixisenatide application follows discussions with the U.S. Food and Drug Administration (FDA) regarding its proposed process for the review of interim data. Sanofi believes that potential public disclosure of early interim data, even with safeguards, could potentially compromise the integrity of the ongoing ELIXA study. Sanofi’s decision is not related to safety issues or deficiencies in the NDA………………………read all at

http://www.pharmalive.com/sanofi-pulls-diabetes-drug-nda

 

EU

US20070037807 * 29 Oct 2004 15 Feb 2007 Satoru Oi Pyridine compounds as inhibitors of dipeptidyl peptidase IV
US20070191436 * 12 Sep 2006 16 Aug 2007 Valerie Niddam-Hildesheim Diastereomeric purification of rosuvastatin
EP0708179A2 * 13 Oct 1995 24 Apr 1996 Eli Lilly And Company Glucagon-like insulinotropic peptide analogs, compositions, and methods of use
Citing Patent Filing date Publication date Applicant Title
CN102584982A * 10 Feb 2012 18 Jul 2012 深圳翰宇药业股份有限公司 Method for purifying solid-phase synthetic coarse liraglutide
WO2013117135A1 * 29 Jan 2013 15 Aug 2013 Hybio Pharmaceutical Co., Ltd. Method for purifying solid-phase synthetic crude liraglutide
WO2014077802A1 * 13 Nov 2012 22 May 2014 Ipsen Pharma S.A.S. Purification method of a glp-1 analogue
WO2014118797A1 1 Jul 2013 7 Aug 2014 Neuland Health Sciences Private Limited Purification of organic compounds using surrogate stationary phases on reversed phase columns
CN1839155A 18. Aug. 2004 27. Sept. 2006 诺沃挪第克公司 Purification of glucagon-like peptides
WO2006041945A2 4. Okt. 2005 20. Apr. 2006 Novetide, Ltd. A counterion exchange process for peptides

References

  1.  Christensen, M; Knop, FK; Holst, JJ; Vilsboll, T (2009). “Lixisenatide, a novel GLP-1 receptor agonist for the treatment of type 2 diabetes mellitus”. IDrugs : the investigational drugs journal 12 (8): 503–13. PMID 19629885.
  2.  “Sanofi New Drug Application for Lixisenatide Accepted for Review by FDA”. Drugs.com/PR Newsire. 19 February 2013.
  3.  “International Nonproprietary Names for Pharmaceutical Substances (INN). Recommended INN: List 61” (PDF). WHO Drug Information 23 (1): 66f. 2009.
Lixisenatide
Clinical data
Trade names Lyxumia
License data
Routes of
administration
Subcutaneous injection
Legal status
Legal status
  • UK: POM (Prescription only)
Identifiers
CAS Number 827033-10-3
ATC code A10BX10 (WHO)
PubChem CID 16139342
IUPHAR/BPS 7387
ChemSpider 17295846
ChEBI CHEBI:85662
Chemical data
Formula C215H347N61O65S
Molar mass 4858.49 g/mol

///////FDA 2016, SANOFI, FDA,  approves , Adlyxin, lixisenatide, type 2 diabetes, Sanofi-Aventis U.S. LLC, Bridgewater, New Jersey, Lyxumia,  利西拉, PEPTIDE, 

CCC(C)C(C(=O)NC(CCC(=O)O)C(=O)NC(Cc1c[nH]c2c1cccc2)C(=O)NC(CC(C)C)C(=O)NC(CCCCN)C(=O)NC(CC(=O)N)C(=O)NCC(=O)NCC(=O)N3CCCC3C(=O)NC(CO)C(=O)NC(CO)C(=O)NCC(=O)NC(C)C(=O)N4CCCC4C(=O)N5CCCC5C(=O)NC(CO)C(=O)NC(CCCCN)C(=O)NC(CCCCN)C(=O)NC(CCCCN)C(=O)NC(CCCCN)C(=O)NC(CCCCN)C(=O)NC(CCCCN)C(=O)N)NC(=O)C(Cc6ccccc6)NC(=O)C(CC(C)C)NC(=O)C(CCCNC(=N)N)NC(=O)C(C(C)C)NC(=O)C(C)NC(=O)C(CCC(=O)O)NC(=O)C(CCC(=O)O)NC(=O)C(CCC(=O)O)NC(=O)C(CCSC)NC(=O)C(CCC(=O)N)NC(=O)C(CCCCN)NC(=O)C(CO)NC(=O)C(CC(C)C)NC(=O)C(CC(=O)O)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C(Cc7ccccc7)NC(=O)C(C(C)O)NC(=O)CNC(=O)C(CCC(=O)O)NC(=O)CNC(=O)C(Cc8cnc[nH]8)N

AND

CCC(C)C(C(=O)NC(CCC(=O)O)C(=O)NC(CC1=CNC2=CC=CC=C21)C(=O)NC(CC(C)C)C(=O)NC(CCCCN)C(=O)NC(CC(=O)N)C(=O)NCC(=O)NCC(=O)N3CCCC3C(=O)NC(CO)C(=O)NC(CO)C(=O)NCC(=O)NC(C)C(=O)N4CCCC4C(=O)N5CCCC5C(=O)NC(CO)C(=O)NC(CCCCN)C(=O)NC(CCCCN)C(=O)NC(CCCCN)C(=O)NC(CCCCN)C(=O)NC(CCCCN)C(=O)NC(CCCCN)C(=O)N)NC(=O)C(CC6=CC=CC=C6)NC(=O)C(CC(C)C)NC(=O)C(CCCNC(=N)N)NC(=O)C(C(C)C)NC(=O)C(C)NC(=O)C(CCC(=O)O)NC(=O)C(CCC(=O)O)NC(=O)C(CCC(=O)O)NC(=O)C(CCSC)NC(=O)C(CCC(=O)N)NC(=O)C(CCCCN)NC(=O)C(CO)NC(=O)C(CC(C)C)NC(=O)C(CC(=O)O)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C(CC7=CC=CC=C7)NC(=O)C(C(C)O)NC(=O)CNC(=O)C(CCC(=O)O)NC(=O)CNC(=O)C(CC8=CN=CN8)N

FDA approves new medication for dry eye disease, Xiidra (lifitegrast ophthalmic solution)


lifitegrast

 

Xiidra (lifitegrast ophthalmic solution)

07/12/2016 08:48 AM EDT
The U.S. Food and Drug Administration approved Xiidra (lifitegrast ophthalmic solution) for the treatment of signs and symptoms of dry eye disease, on Monday, July 11, 2016. Xiidra is the first medication in a new class of drugs, called lymphocyte function-associated antigen 1 (LFA-1) agonist, approved by the FDA for dry eye disease.

FDA approves new medication for dry eye disease

July 12, 2016

Release

The U.S. Food and Drug Administration approved Xiidra (lifitegrast ophthalmic solution) for the treatment of signs and symptoms of dry eye disease, on Monday, July 11, 2016. Xiidra is the first medication in a new class of drugs, called lymphocyte function-associated antigen 1 (LFA-1) agonist, approved by the FDA for dry eye disease.

“Normal tear production is needed for clear vision and eye health,” said Edward Cox, M.D., director of the Office of Antimicrobial Products in the FDA’s Center for Drug Evaluation and Research. “This approval will provide a new treatment option for patients with dry eye disease.”

Dry eye disease includes a group of conditions in which the eye does not produce an adequate volume of tears or when the tears are not of the correct consistency. The chance of experiencing dry eye increases with age, affecting approximately five percent of the adult population age 30-40 and 10 to 15 percent of adults over age 65, and is more common among women. When severe and left untreated, this condition can lead to pain, ulcers or scars on the part of the eye called the cornea. Dry eye can make it more difficult to perform some activities, such as using a computer or reading for an extended period of time, and it can decrease tolerance for dry environments, such as the air inside an airplane.

The safety and efficacy of Xiidra was assessed in over a thousand patients, in four separate, randomized, controlled studies. These studies included patients 19–97 years of age, of which the majority were female (76 percent). Patients were randomized equally to receive either Xiidra eyedrops or placebo eyedrops, which were used twice a day for twelve weeks. The studies found that groups treated with Xiidra demonstrated more improvement in both the signs and the symptoms of eye dryness than the groups treated with placebo.

The most common side effects of Xiidra include eye irritation, discomfort or blurred vision and an unusual taste sensation (dysgeusia).

Dry eye disease does not routinely occur in children. Safety and efficacy in pediatric patients below the age of 17 years has not been studied.

Xiidra is manufactured by Shire US Inc., of Lexington, Massachusetts.

ref https://newdrugapprovals.org/2014/09/04/lifitegrast-sar-1118-effective-inhibitor-of-lfa-1-interactions-with-icam-1/

Common name: Lifitegrast, SAR 1118

Trademarks: Lifitegrast
Molecular Formula: C29H24Cl2N2O7S
CAS Registry Number: 1025967-78-5
Molecular Weight: 615.49
Activity: SAR 1118 is a potent novel small molecule lymphocyte function-associated antigen-1 (LFA-1/ICAM-1) antagonist for a broad range of ocular inflammatory conditions including dry eye and diabetic macular edema.
Intermediates:
Lifitegrast Synthesis: US20110092707A1
References:
1. Burnier, J. Crystalline Pharmaceutical and Methods of Preparation and Use Thereof. US20110092707A1
2. Zhong, M.; et. al. Discovery of tetrahydroisoquinoline (THIQ) derivatives as potent and orally bioavailable LFA-1/ICAM-1 antagonists. Bioorg. Med. Chem. Lett. 20 (2010) 5269-5273.
3. Zeller, J. R.; et. al. Lfa-1 inhibitor and polymorph thereof. WO2014018748A1
4. Zhong, M.; et. al. Modulators of cellular adhesion. WO2005044817A1
///////Xiidra,  Shire US Inc., Lexington, Massachusetts,  fda 2016, lifitegrast ophthalmic solution, FDA,  approves,  new medication , dry eye disease

FDA approves new drug Venclexta (venetoclax) for chronic lymphocytic leukemia in patients with a specific chromosomal abnormality


Venetoclax.svg
Venclexta (venetoclax)
 .
 .
 .
04/11/2016 12:12 PM EDT
The U.S. Food and Drug Administration today approved Venclexta (venetoclax) for the treatment of patients with chronic lymphocytic leukemia (CLL) who have a chromosomal abnormality called 17p deletion and who have been treated with a least one prior therapy. Venclexta is the first FDA-approved treatment that targets the B-cell lymphoma 2 (BCL-2) protein, which supports cancer cell growth and is overexpressed in many patients with CLL.

April 11, 2016

Release

The U.S. Food and Drug Administration today approved Venclexta (venetoclax) for the treatment of patients with chronic lymphocytic leukemia (CLL) who have a chromosomal abnormality called 17p deletion and who have been treated with at least one prior therapy. Venclexta is the first FDA-approved treatment that targets the B-cell lymphoma 2 (BCL-2) protein, which supports cancer cell growth and is overexpressed in many patients with CLL.

According to the National Cancer Institute, CLL is one of the most common types of leukemia in adults, with approximately 15,000 new cases diagnosed each year. CLL is characterized by the progressive accumulation of abnormal lymphocytes, a type of white blood cell. Patients with CLL who have a 17p deletion lack a portion of the chromosome that acts to suppress cancer growth. This chromosomal abnormality occurs in approximately 10 percent of patients with untreated CLL and in approximately 20 percent of patients with relapsed CLL.

“These patients now have a new, targeted therapy that inhibits a protein involved in keeping tumor cells alive,” said Richard Pazdur, director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research. “For certain patients with CLL who have not had favorable outcomes with other therapies, Venclexta may provide a new option for their specific condition.”

The efficacy of Venclexta was tested in a single-arm clinical trial of 106 patients with CLL who have a 17p deletion and who had received at least one prior therapy. Trial participants took Venclexta orally every day, beginning with 20 mg and increasing over a five-week period to 400 mg. Results showed that 80 percent of trial participants experienced a complete or partial remission of their cancer.

Venclexta is indicated for daily use after detection of 17p deletion is confirmed through the use of the FDA-approved companion diagnostic Vysis CLL FISH probe kit.

The most common side effects of Venclexta include low white blood cell count (neutropenia), diarrhea, nausea, anemia, upper respiratory tract infection, low platelet count (thrombocytopenia) and fatigue. Serious complications can include pneumonia, neutropenia with fever, fever, autoimmune hemolytic anemia, anemia and metabolic abnormalities known as tumor lysis syndrome. Live attenuated vaccines should not be given to patients taking Venclexta.

The FDA granted the Venclexta application breakthrough therapy designation, priority review status, and accelerated approval for this indication. These are distinct programs intended to facilitate and expedite the development and review of certain new drugs in light of their potential to benefit patients with serious or life-threatening conditions. Venclexta also received orphan drug designation, which provides incentives such as tax credits, user fee waivers and eligibility for exclusivity to assist and encourage the development of drugs for rare diseases.

Venclexta is manufactured by AbbVie Inc. of North Chicago, Illinois, and marketed by AbbVie and Genentech USA Inc. of South San Francisco, California. The Vysis CLL FISH probe kit is manufactured by Abbott Molecular of Des Plaines, Illinois.

///FDA,  approves,  new drug, chronic lymphocytic leukemia,  specific chromosomal abnormality, Venclexta, venetoclax,  fda 2016

FDA approves new treatment for HIV


11/05/2015 12:53 PM EST
The U.S. Food and Drug Administration today approved Genvoya (a fixed-dose combination tablet containing elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide) as a complete regimen for the treatment of HIV-1 infection in adults and pediatric patients 12 years of age and older

http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm471300.htm?source=govdelivery&utm_medium=email&utm_source=govdelivery

November 5, 2015

Release

The U.S. Food and Drug Administration today approved Genvoya (a fixed-dose combination tablet containing elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide) as a complete regimen for the treatment of HIV-1 infection in adults and pediatric patients 12 years of age and older.

The CDC estimates that 1.2 million persons ages 13 years and older are living with HIV infection, and that more than another 150,000 persons in this age range have HIV but are unaware of their infection. Over the past decade, the number of people living with HIV has increased, while the annual number of new HIV infections has remained relatively stable.

“Today’s approval of a fixed dose combination containing a new form of tenofovir provides another effective, once daily complete regimen for patients with HIV-1 infection,” said Edward Cox, M.D., director of the Office of Antimicrobial Products in the FDA’s Center for Drug Evaluation and Research.

Genvoya is approved for use in HIV-infected adults and children ages 12 years and older weighing at least 35 kilograms (77 pounds) who have never taken HIV therapy (treatment-naïve) and HIV-infected adults whose HIV-1 virus is currently suppressed. While Genvoya is not recommended for patients with severe renal impairment, those with moderate renal impairment can take Genvoya.

Genvoya’s safety and efficacy in adults were evaluated in 3,171 participants enrolled in four clinical trials. Depending on the trial, participants were randomly assigned to receive Genvoya or another FDA approved HIV treatment. Results showed Genvoya was effective in reducing viral loads and comparable to the other treatment regimens.

Genvoya contains a new form of tenofovir that has not been previously approved. This new form of tenofovir provides lower levels of drug in the bloodstream, but higher levels within the cells where HIV-1 replicates. It was developed to help reduce some drug side effects. Genvoya appears to be associated with less kidney toxicity and decreases in bone density than previously approved tenofovir containing regimens based on laboratory measures. Patients receiving Genvoya experienced greater increases in serum lipids (total cholesterol and low-density lipoprotein) than patients receiving other treatment regimens in the studies.

Genvoya carries a Boxed Warning alerting patients and health care providers that the drug can cause a buildup of lactic acid in the blood and severe liver problems, both of which can be fatal. The Boxed Warning also states that Genvoya is not approved to treat chronic hepatitis B virus infection. The most common side effect associated with Genvoya is nausea. Serious side effects include new or worsening kidney problems, decreased bone mineral density, fat redistribution and changes in the immune system (immune reconstitution syndrome). Health care providers are advised to monitor patients for kidney and bone side effects. Genvoya should not be given with other antiretroviral products and may have drug interactions with a number of other commonly used medications.

Genvoya is marketed by Gilead Sciences Inc. based in Foster City, California.

/////////

EMA approves AstraZeneca’s lesinurad to treat gout patients


EMA approves AstraZeneca’s lesinurad to treat gout patients
British-Swedish drugmaker AstraZeneca has received approval from European Medicines Agency (EMA) for its lesinurad 200mg tablets to treat gout patients. READ AT…..[LINK]

 

 

SYNTHESIS………..https://newdrugapprovals.org/2013/03/13/phase-3-ongoing-lesinurad-monotherapy-in-gout-subjects-intolerant-to-xanthine-oxidase-inhibitors-light/

“The company submitted a MAA based on data from the Clear1, Clear2 and Crystal pivotal Phase III combination therapy studies.”

AstraZeneca’s subsidiary Ardea Biosciences carried out Clear1, Clear2 and Crystal trials.

 

LESINURAD

SYNTHESIS………..https://newdrugapprovals.org/2013/03/13/phase-3-ongoing-lesinurad-monotherapy-in-gout-subjects-intolerant-to-xanthine-oxidase-inhibitors-light/

FDA Approves Vitekta (elvitegravir) for HIV-1 Infection


FDA Approves Vitekta (elvitegravir) for HIV-1 Infection

September 24, 2014 — The U.S. Food and Drug Administration (FDA) has approved Vitekta (elvitegravir), an integrase strand transfer inhibitor for the combination treatment of human immunodeficiency virus type 1 (HIV-1) infection in treatment-experienced adults.

 http://www.drugs.com/newdrugs/fda-approves-vitekta-elvitegravir-hiv-1-infection-4089.html?utm_source=ddc&utm_medium=email&utm_campaign=Today%27s+news+summary+-+September+25%2C+2014

Elvitegravir

697761-98-1 CAS

Elvitegravir (EVG, formerly GS-9137) is a drug used for the treatment of HIV infection. It acts as an integrase inhibitor. It was developed[1] by the pharmaceutical company Gilead Sciences, which licensed EVG from Japan Tobacco in March 2008.[2][3][4] The drug gained approval by U.S. Food and Drug Administration on August 27, 2012 for use in adult patients starting HIV treatment for the first time as part of the fixed dose combination known as Stribild.[5]

According to the results of the phase II clinical trial, patients taking once-daily elvitegravir boosted by ritonavir had greater reductions in viral load after 24 weeks compared to individuals randomized to receive a ritonavir-boosted protease inhibitor.[6]


 Human immunodeficiency virus type 1 (HIV-1) is the causative agent of acquired immunodeficiency disease syndrome (AIDS).  After over 26 years of efforts, there is still not a therapeutic cure or an effective vaccine against HIV/AIDS.  The clinical management of HIV-1 infected people largely relies on antiretroviral therapy (ART).  Although highly active antiretroviral therapy (HAART) has provided an effective way to treat AIDS patients, the huge burden of ART in developing countries, together with the increasing incidence of drug resistant viruses among treated people, calls for continuous efforts for the development of anti-HIV-1 drugs.  Currently, four classes of over 30 licensed antiretrovirals (ARVs) and combination regimens of these ARVs are in use clinically including: reverse transcriptase inhibitors (RTIs) (e.g. nucleoside reverse transcriptase inhibitors, NRTIs; and non-nucleoside reverse transcriptase inhibitors, NNRTIs), protease inhibitors (PIs), integrase inhibitors and entry inhibitors (e.g. fusion inhibitors and CCR5 antagonists).

  1.  Gilead Press Release Phase III Clinical Trial of Elvitegravir July 22, 2008
  2.  Gilead Press Release Gilead and Japan Tobacco Sign Licensing Agreement for Novel HIV Integrase Inhibitor March 22, 2008
  3.  Shimura K, Kodama E, Sakagami Y, et al. (2007). “Broad Anti-Retroviral Activity and Resistance Profile of a Novel Human Immunodeficiency Virus Integrase Inhibitor, Elvitegravir (JTK-303/GS-9137)”J Virol 82 (2): 764. doi:10.1128/JVI.01534-07PMC 2224569PMID 17977962.
  4.  Stellbrink HJ (2007). “Antiviral drugs in the treatment of AIDS: what is in the pipeline ?”. Eur. J. Med. Res. 12 (9): 483–95. PMID 17933730.
  5.  Sax, P. E.; Dejesus, E.; Mills, A.; Zolopa, A.; Cohen, C.; Wohl, D.; Gallant, J. E.; Liu, H. C.; Zhong, L.; Yale, K.; White, K.; Kearney, B. P.; Szwarcberg, J.; Quirk, E.; Cheng, A. K.; Gs-Us-236-0102 Study, T. (2012). “Co-formulated elvitegravir, cobicistat, emtricitabine, and tenofovir versus co-formulated efavirenz, emtricitabine, and tenofovir for initial treatment of HIV-1 infection: A randomised, double-blind, phase 3 trial, analysis of results after 48 weeks”.The Lancet 379 (9835): 2439–2448. doi:10.1016/S0140-6736(12)60917-9PMID 22748591edit
  6.  Thaczuk, Derek and Carter, Michael. ICAAC: Best response to elvitegravir seen when used with T-20 and other active agents Aidsmap.com. 19 Sept. 2007.

 

 The life cycle of HIV-1.  1. HIV-1 gp120 binds to CD4 and co-receptor CCR5/CXCR4 on target cell; 2. HIV-1 gp41 mediates fusion with target cell; 3. Nucleocapsid containing viral genome and enzymes enters cells; 4. Viral genome and enzymes are released; 5. Viral reverse transcriptase catalyzes reverse transcription of ssRNA, forming RNA-DNA hybrids; 6. RNA template is degraded by ribonuclease H followed by the synthesis of HIV dsDNA; 7. Viral dsDNA is transported into the nucleus and integrated into the host chromosomal DNA by the viral integrase enzyme; 8. Transcription of proviral DNA into genomic ssRNA and mRNAs formation after processing; 9. Viral RNA is exported to cytoplasm; 10. Synthesis of viral precursor proteins under the catalysis of host-cell ribosomes; 11. Viral protease cleaves the precursors into viral proteins; 12. HIV ssRNA and proteins assemble under host cell membrane, into which gp120 and gp41 are inserted; 13. Membrane of host-cell buds out, forming the viral envelope; 14. Matured viral particle is released

Elvitegravir, also known as GS 9137 or JTK 303, is an investigational new drug and a novel oral integrase inhibitor that is being evaluated for the treatment of HIV-1 infection. After HIVs genetic material is deposited inside a cell, its RNA must be converted (reverse transcribed) into DNA. A viral enzyme called integrase then helps to hide HIVs DNA inside the cell’s DNA. Once this happens, the cell can begin producing genetic material for new viruses. Integrase inhibitors, such as elvitegravir, are designed to block the activity of the integrase enzyme and to prevent HIV DNA from entering healthy cell DNA. Elvitegravir has the chemical name: 6-(3-chloro-2-fluorobenzyl)-1-[(S)-1 -hydroxy -methyl-2- methylpropyl]-7-methoxy-4-oxo-1, 4-dihydroquinoline-3-carboxylic acid and has the following structural formula:

Figure imgf000002_0001

WO 2000040561 , WO 2000040563 and WO 2001098275 disclose 4-oxo-1 , 4-dihydro-3- quinoline which is useful as antiviral agents. WO2004046115 provides certain 4- oxoquinoline compounds that are useful as HIV Integrase inhibitors.

US 7176220 patent discloses elvitegravir, solvate, stereoisomer, tautomer, pharmaceutically acceptable salt thereof or pharmaceutical composition containing them and their method of treatment. The chemistry involved in the above said patent is depicted below in the Scheme A. Scheme-A

Toluene, DIPEA

SOCl2 ,COCl (S)-(+)-Valinol

Toluene

Figure imgf000003_0001

,4-Difluoro-5-iodo- benzoic acid

Figure imgf000003_0003
Figure imgf000003_0002

THF

dichlorobis(triphenylphosphine)

palladium argon stream,

Figure imgf000003_0004

Elvitegravir Form ] Elvitegravir (residue) US 7635704 patent discloses certain specific crystalline forms of elvitegravir. The specific crystalline forms are reported to have superior physical and chemical stability compared to other physical forms of the compound. Further, process for the preparation of elvitegravir also disclosed and is depicted below in the Scheme B. The given processes involve the isolation of the intermediates at almost all the stages.

Scheme B

2,

Figure imgf000004_0001

Zn THF,

CK Br THF CU “ZnBr dιchlorobis(trιphenylphos

phine)palladium

Figure imgf000004_0002

Elvitegravir WO 2007102499 discloses a compound which is useful as an intermediate for the synthesis of an anti-HIV agent having an integrase-inhibiting activity; a process for production of the compound; and a process for production of an anti-HIV agent using the intermediate.

WO 2009036161 also discloses synthetic processes and synthetic intermediates that can be used to prepare 4-oxoquinolone compounds having useful integrase inhibiting properties.

The said processes are tedious in making and the purity of the final compound is affected because of the number of steps, their isolation, purification etc., thus, there is a need for new synthetic methods for producing elvitegravir which process is cost effective, easy to practice, increase the yield and purity of the final compound, or that eliminate the use of toxic or costly reagents.

US Patent No 7176220 discloses Elvitegravir, solvate, stereoisomer, tautomer, pharmaceutically acceptable salt thereof or pharmaceutical composition containing them and ■ their method of treatment. US Patent No 7635704 discloses Elvitegravir Form II, Form III and processes for their preparation. The process for the preparation of Form Il disclosed in the said patent is mainly by three methods – a) dissolution of Elvitegravir followed by seeding with Form II, b) recrystallisation of Elvitegravir, and c) anti-solvent method.

The process for the preparation of Form III in the said patent is mainly by three methods – a) dissolution of Form Il in isobutyl acetate by heating followed by cooling the reaction mass, b) dissolution of Form Il in isobutyl acetate by heating followed by seeding with Form III, and c) dissolving Form Il in 2-propanol followed by seeding with Form III.

Amorphous materials are becoming more prevalent in the pharmaceutical industry. In order to overcome the solubility and potential bioavailability issues, amorphous solid forms are becoming front-runners. Of special importance is the distinction between amorphous and crystalline forms, as they have differing implications on drug substance stability, as well as drug product stability and efficacy.

An estimated 50% of all drug molecules used in medicinal therapy are administered as salts. A drug substance often has certain suboptimal physicochemical or biopharmaceutical properties that can be overcome by pairing a basic or acidic drug molecule with a counter- ion to create a salt version of the drug. The process is a simple way to modify the properties of a drug with ionizable functional groups to overcome undesirable features of the parent drug. Salt forms of drugs have a large effect on the drugs’ quality, safety, and performance. The properties of salt-forming species significantly affect the pharmaceutical properties of a drug and can greatly benefit chemists and formulators in various facets of drug discovery and development.

Figure imgf000020_0003

chemical synthesis from a carboxylic acid 1 starts after conversion to the acid chloride iodide NIS 2 , and with three condensation 4 . 4 and the amino alcohol 5 addition-elimination reaction occurs 6 , 6 off under alkaline conditions with TBS protected hydroxy get the ring 7 , 7 and zinc reagent 8 Negishi coupling occurs to get 9 , the last 9 hydrolysis and methoxylated

Egypt for Raltegravir (Elvitegravir) -2012 August of anti-AIDS drugs approved by the FDA

Elvitegravir dimer impurity, WO2011004389A2

Isolation of 1-[(2S)-1-({3-carboxy-6-(3-chloro-2-fluorobenzyl)-1 -[(2S)-I- hydroxy-3-methylbutan-2-yl]-4-oxo-1 , 4-dihydroquinolin-7-yl}oxy)-3- methylbutan-2-yl 6-(3-chloro-2-fluorobenzyl)-7-methoxy-4-oxo-1 , 4-dihydroquinoline-3-carboxylic acid (elvitegravir dimer impurity, 13)

After isolation of the elvitegravir from the mixture of ethyl acetate-hexane, solvent from the filtrate was removed under reduced pressure. The resultant residue purified by column chromatography using a mixture of ethyl acetate-hexane (gradient, 20-80% EtOAc in hexane) as an eluent. Upon concentration of the required fractions, a thick solid was obtained which was further purified on slurry washing with ethyl acetate to get pure elvitegravir dimer impurity (13). The 1H-NMR, 13C-NMR and mass spectral data complies with proposed structure.

Figure imgf000041_0001

1H-NMR (DMSO-Cf6, 300 MHz, ppm) – δ 0.79 (m, d=6.3 Hz, 6H, 20 & 2O’)\ 1.18 & 1.20 (d, J=6.3 Hz & J=6.2 Hz, 6H, 21 & 21′)1, 2.42-2.49 (m, 2H, 19 & 19′), 3.81-3.89 (m, 3H, T & 17’Ha), 3.94-4.01 (m, 1 H, 17’Hb), 4.01 (s, 3H, 23), 4.11 (s, 2H, 7), 4.83-4.85 (m, 3H, 17 & 18′), 5.22 (t, J=4.7 Hz, 1H, OH), 5.41-5.44 (m, 1 H, 18), 6.73-6.78 (t, J=7.1 Hz, 1 H, 11)1‘ 2, 6.92-6.98 (t, J=8.0 Hz, 1H, 3′) 12, 7.12-7.22 (m, 2H, 1 & 3), 7.34-7.39 (m, 1H, 2′),

7.45-7.48 (m, 1 H, 2), 7.49, 7.56 (s, 2H, 15 & 15′), 7.99, 8.02 (s, 2H, 9 & 9′), 8.89, 9.01 (s, 2H, 13 & 13′), 15.30, 15.33 (s, 2H, COOH’ & COOH”).

13C-NMR (DMSO-Cf6, 75 MHz, ppm)- δ 18.87, 19.03 (2OC, 20’C), 19.11 , 19.24 (21 C, 21 ‘C), 27.94 (7’C), 28.40 (7C), 28.91 , 30.08 (19C, 19’C), 56.80(23C), 60.11 (171C), 63.59 (18C), 66.52 (18’C), 68.53 (17C), 97.86, 98.97 (15, 15′), 107.43, 108.16 (12C, 12’C),

118.77, 119.38 (1OC, 10’C), 119.57 (d, J=17.6 Hz, 41C), 119.61 (d, J=17.9 Hz, 4C),

124.88 (d, J=4.3 Hz, 31C), 125.18 (d, J=4.2 Hz, 3C), 126.59, 126.96 (9C1 9’C), 127.14 (8’C), 127.62 (d, J=15.9 Hz, 61C), 127.73 (8C), 127.99 (d, J=15.2 Hz, 6C), 128.66 (2’C),

128.84 (11C), 128.84 (2C), 130.03 (d, J=3.4 Hz, 1C), 142.14, 142.44 (14C, 14’C), 144.37, 145.56 (13C, 131C), 155.24 (d, J=245.1 Hz, 5’C)1 155.61 (d, J=245.1 Hz, 5C),

160.17 (16’C), 162.04 (16C), 166.00, 166.14 (22C, 22’C), 176.17, 176.22 (11C, 111C).

DIP MS: m/z (%)- 863 [M+H]+, 885 [M+Na]+.

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FDA Approves Trulicity (dulaglutide) for Type 2 Diabetes


FDA Approves Trulicity (dulaglutide) for Type 2 Diabetes

 

DULAGLUTIDE
PRONUNCIATION doo” la gloo’ tide
THERAPEUTIC CLAIM Treatment of type II diabetes
CHEMICAL NAMES
1. 7-37-Glucagon-like peptide I [8-glycine,22-glutamic acid,36-glycine] (synthetic
human) fusion protein with peptide (synthetic 16-amino acid linker) fusion protein with immunoglobulin G4 (synthetic human Fc fragment), dimer
2. [Gly8,Glu22,Gly36]human glucagon-like peptide 1-(7-37)-peptidyltetraglycyl-Lseryltetraglycyl-L-seryltetraglycyl-L-seryl-L-alanyldes-Lys229-[Pro10,Ala16,Ala17]human immunoglobulin heavy constant γ4 chain H-CH2-CH3 fragment, (55-55′:58-58′)-bisdisulfide dimer

 

  • Dulaglutide
  • LY 2189265
  • LY-2189265
  • LY2189265
  • UNII-WTT295HSY5

 

GLP-1 immunoglobulin G (IgG4) Fc fusion protein with extended activity; a hypoglycemic agent.
  • 7-37-Glucagon-like peptide I (8-glycine,22-glutamic acid,36-glycine) (synthetic human) fusion protein
    with peptide (synthetic 16-amino acid linker) fusion protein with immunoglobulin G4 (synthetic human Fc fragment), dimer

 

sept 18 2014

The US Food and Drug Administration (FDA) has approved dulaglutide (Trulicity, Eli Lilly & Co), as a once-weekly injection for the treatment of type 2 diabetes.

A member of the glucagon-like peptide-1 receptor agonist class, dulaglutide joins liraglutide (Victoza, Novo Nordisk), exenatide (Byetta, AstraZeneca/Bristol-Myers Squibb), and albiglutide (Tanzeum, GlaxoSmithKline), on the US market.

Once-weekly dulaglutide was approved based on 6 clinical trials involving a total of 3342 patients who received the drug. It was studied as a stand-alone therapy and in combination withmetformin, sulfonylurea, thiazolidinedione, and prandial insulin.

In one trial the once-weekly dulaglutide was non-inferior to daily liraglutide and in another it topped the oral dipeptidyl peptidase-4 (DPP-4) inhibitor sitagliptin (Januvia, Merck).

The most common side effects observed in patients treated with dulaglutide were nausea, diarrhea, vomiting, abdominal pain, and decreased appetite.

Dulaglutide should not be used to treat people with type 1 diabetes, diabetic ketoacidosis, or severe abdominal or intestinal problems, or as first-line therapy for patients who cannot be managed with diet and exercise.

As with others in its class, dulaglutide’s label will include a boxed warning that thyroid C-cell tumors have been observed in rodents but the risk in humans is unknown. The drug should not be used in patients with a personal or family history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia type 2.

The FDA is requiring Lilly to conduct the following postmarketing studies for dulaglutide:

•  A clinical trial to evaluate dosing, efficacy, and safety in children

•  A study to assess potential effects on sexual maturation, reproduction, and central nervous system development and function in immature rats

•  An MTC case registry of at least 15 years duration to identify any increase in MTC incidence with the drug

•  A clinical trial comparing dulaglutide with insulin glargine on glycemic control in patients with type 2 diabetes and moderate or severe renal impairment

•  A cardiovascular outcomes trial to evaluate the drug’s cardiovascular risk profile in patients with high baseline risk for cardiovascular disease.

The FDA approval also comes with a Risk Evaluation and Mitigation Strategy, including a communication plan to inform healthcare professionals about the serious risks associated with the drug.

 

 

STRUCTURAL FORMULA
Monomer
HGEGTFTSDV SSYLEEQAAK EFIAWLVKGG GGGGGSGGGG SGGGGSAESK 50
YGPPCPPCPA PEAAGGPSVF LFPPKPKDTL MISRTPEVTC VVVDVSQEDP 100
EVQFNWYVDG VEVHNAKTKP REEQFNSTYR VVSVLTVLHQ DWLNGKEYKC 150
KVSNKGLPSS IEKTISKAKG QPREPQVYTL PPSQEEMTKN QVSLTCLVKG 200
FYPSDIAVEW ESNGQPENNY KTTPPVLDSD GSFFLYSRLT VDKSRWQEGN 250
VFSCSVMHEA LHNHYTQKSL SLSLG 275
Disulfide bridges location
55-55′ 58-58′ 90-150 90′-150′ 196-254 196′-254′
MOLECULAR FORMULA C2646H4044N704O836S18
MOLECULAR WEIGHT 59.67 kDa

MANUFACTURER Eli Lilly and Company
CODE DESIGNATION LY2189265
CAS REGISTRY NUMBER 923950-08-7

http://www.ama-assn.org/resources/doc/usan/dulaglutide.pdf

LY2189265 (dulaglutide), a glucagon-like peptide-1 analog, is a biologic entity being studied as a once-weekly treatment for type 2 diabetes.

Dulaglatuide works by stimulating cells to release insulin only when blood sugar levels are high.

Gwen Krivi, Ph.D., vice president, product development, Lilly Diabetes, said of the drug, “We believe dulaglutide, if approved, can bring significant benefits to people with type 2 diabetes.”

In fact, it might help to control both diabetics’ blood sugar and their high blood pressure.

Eli Lilly CEO John Lechleiter believes the drug has the potential to be a blockbuster. Lilly could be ready to seek approval by 2013.

For more information on dulaglutide clinical studies, click here.

 

 

PRESS RELEASES

Data Preseted at 49th EASD Annual Meeting Show Treatment with Lilly’s Investigational Dulaglutide Resulted in Improved Patient-Reported Health Outcomes – September 26, 2013

Lilly’s Investigational GLP-1 Receptor Agonist, Dulaglutide, Showed Superior Glycemic Control Versus Comparators in Patients with Type 2 Diabetes – June 22, 2013

Lilly Announces Positive Results of Phase III Trials of Dulaglutide in Type 2 Diabetes – April 16, 2013

Lilly Diabetes Announces Positive Results of Phase III Trials of Dulaglutide in Type 2 Diabetes
 – October 22, 2012

Lilly Diabetes Presents Phase II Blood Pressure and Heart Rate Data on Investigational GLP-1 Analog Candidate, Dulaglutide, in Patients with Type 2 Diabetes at the 27th American Society of Hypertension Scientific Meeting – May 22, 2012

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