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DRUG APPROVALS BY DR ANTHONY MELVIN CRASTO
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Chelsea encouraged by FDA talks on Northera(droxidopa)
(2R,3S)-2-amino-3-(3,4-dihydroxyphenyl)-3-hydroxypropanoic acid
L-DOPS (L-threo-dihydroxyphenylserine; Droxidopa; SM-5688) is a psychoactive drugand synthetic amino acid precursor which acts as a prodrug to the neurotransmittersnorepinephrine (noradrenaline) and epinephrine (adrenaline).[1] Unlike norepinephrine and epinephrine themselves, L-DOPS is capable of crossing the protective blood–brain barrier(BBB).[1]
L-DOPS was developed by Sumitomo Pharmaceuticals under the trade name Droxidopafor the treatment of hypotension, including NOH,[2] and NOH associated with variousdisorders such as MSA, FAP, and PD, as well as IDH. The drug has been used in Japanand some surrounding Asian areas for these indications since 1989. Following a merge with Dainippon Pharmaceuticals in 2006, Dainippon Sumitomo Pharma licensed L-DOPS to Chelsea Therapeutics to develop and market it worldwide except in Japan, Korea, China, and Taiwan.
Clinical trials
Though L-DOPS has been used in Japan and Southeast Asia already for some time, it is also currently in clinical trials at the phase IIIpoint in the United States (U.S.), Canada, Australia, and throughout Europe. Provided L-DOPS successfully completes clinical trials, it could be approved for the treatment of NOH as early as 2011.[4] Additionally, phase II clinical trials for IDH are also underway. Chelsea Therapeutics obtained orphan drug status (ODS) for L-DOPS in the U.S. for NOH, and that of which associated with PD, PAF, and MSA, and is the pharmaceutical company developing it in that country.
FEBRUARY 21, 2013
Shares in Chelsea Therapeutics International have leapt after the company said it will resubmit its previously-rejected treatment of neurogenic orthostatic hypotension, Northera, after helpful discussions with US regulators.
A year ago, the Food and Drug Administration issued Chelsea with a complete response letter asking for more data regarding its filing for Northera (droxidopa)for NOH. That came as something of a surprise given that the agency’s Cardiovascular and Renal Drugs Advisory Committee had earlier voted 7-4 in favour of the therapy.
Now Chelsea says that following a meeting, it has received written guidance from the Director of the Office of New Drugs at the FDA stating that an ongoing study has the potential to serve as the basis for a resubmission.
The guidance suggests that “data strongly demonstrating a short-term clinical benefit of droxidopa in patients with NOH would be adequate for approval, with a possible requirement to verify durable clinical benefit post-approval”.
Encouraged by this, Chelsea plans to refile Northera in the late second quarter of 2013. Chief executive Joseph Oliveto said the firm looks forward to submitting the totality of our clinical experience to date to the agency for review…we now have a regulatory path forward”.
Chelsea also intends to initiate a new clinical trial in the fourth quarter of 2013.
- Goldstein, DS (2006). “L-Dihydroxyphenylserine (L-DOPS): a norepinephrine prodrug”. Cardiovasc Drug Rev 24 (3-4): 189–203. doi:10.1111/j.1527-3466.2006.00189.x.PMID 17214596.
- Mathias, Christopher J (2008). “L-dihydroxyphenylserine (Droxidopa) in the treatment of orthostatic hypotension”. Clin Auton Res 18 (Supplement 1): 25–29. doi:10.1007/s10286-007-1005-z.
- Crofford, LJ (2008). “Pain management in fibromyalgia”. Curr Opin Rheumatol 20 (3): 246–250.doi:10.1097/BOR.0b013e3282fb0268. PMID 18388513.
- Search of: “Droxidopa” – List Results – ClinicalTrials.gov
- Robertson, David (2008). “The pathophysiology and diagnosis of orthostatic hypotension”. Clin Auton Res 18(Supplement 1): 2–7. doi:10.1007/s10286-007-1004-0.
ONO Pharmaceutcal files for approval of Additional Indication for Onoact® 50 injection, Short-Acting Selective β1 Blocker in Japan
disease. AF/AFL with LV dysfunction accompanying by persistent elevated heart rate would lead to further deterioration of cardiac performance. Swift rate control is inevitable to be restored from this detrimental condition, however, no drug on market can provide both the features of fast-acting and easy titratability for tachyarrhythmia (AF/AFL) with LV dysfunction.
Onoact® 50 for injection is the short-acting selective β1 blocker which reduces heart rate by selectively blocking β1 receptors located chiefly in the heart and this fast-acting drug can be easily titrated.
We expect that Onoact® 50 for injection can contribute to promptly reducing heart rate without causing deterioration of cardiac performance in treatment of tachyarrhythmia (AF/AFL) with LV dysfunction.
This short-acting selective β1 blocker drug is discovered and developed by ONO and has been widely used by many patients since its launch. The drug has firstly received approval for emergency treatment of intra-operative tachyarrhythmia (atrial fibrillation and flutter, and sinus tachycardia) in July 2002. Then, it had also been approved for additional indication of emergency treatment of post-operative tachyarrhythmia (atrial fibrillation and flutter, and sinus tachycardia) with monitoring of circulatory dynamics in October 2006.
| Identifiers | |
|---|---|
| CAS number | 133242-30-5 |
| Chemical data | |
| Formula | C25H39N3O8 |
| Mol. mass | 509.59 g/mol |
Landiolol (INN) is a drug which acts as a highly cardioselective, ultra short-acting beta blocker. It is used as an anti-arrhythmic agent.
- Yoshiya I (December 1998). “[Landiolol hydrochloride, a new sympathetic beta blocker]” (in Japanese). Masui 47 Suppl: S126–32. PMID 9921175.
- Ogata J, Okamoto T, Minami K (2003). “Landiolol for the treatment of tachyarrhythmia associated with atrial fibrillation”. Can J Anaesth 50 (7): 753. doi:10.1007/BF03018726. PMID 12944459
FDA Approves Natrelle 410 Breast Implant
Silicone gel-filled breast implants
Image/FDA
Feb. 20, 2013
The U.S. Food and Drug Administration (FDA) approved Allergan’s new silicone gel-filled breast implant today, making it the fourth FDA-approved silicone gel-filled breast implant product available in the U.S, according to an FDA news release Feb. 20.
The product, the Natrelle 410 Highly Cohesive Anatomically Shaped Silicone-Gel Filled Breast Implant, can be used increase breast size (augmentation) in women at least 22 years old and to rebuild breast tissue (reconstruction) in women of any age.
According to the FDA, the approval is based on seven years of data from 941 women. Most complications and outcomes reflect those found in previous breast implant studies including tightening of the area around the implant (capsular contracture), re-operation, implant removal, an uneven appearance (asymmetry), and infection.
It’s important to remember that breast implants are not lifetime devices. Women should fully understand the risks associated with breast implants before considering augmentation or reconstruction surgery, and they should recognize that long-term monitoring is essential,” said Jeffrey Shuren, M.D., director of the FDA’s Center for Devices and Radiological Health.
“The data we reviewed showed a reasonable assurance of safety and effectiveness,” said Shuren.
The FDA requires that Allergan conduct a series of post-approval studies to assess long-term safety and effectiveness outcomes and the risks of rare disease.
Edison commences EPI-743 Vatiquinone Phase 2 study in cobalamin C deficient patients
19 February 2013
EPI-743 Vatiquinone is a new drug that is based on vitamin E. Tests have shown that it can help improve the function of cells with mitochondrial problems. It may be able to treat people with genetic disorders that affect metabolism and mitochondria
Edison Pharmaceuticals and Bambino Gesu Children’s Hospital have announced the commencement of EPI-743 Phase 2 cobalamin C deficiency syndrome trial.
EPI-743 is an orally bioavailable small molecule and a member of the para-benzoquinone class of drugs.
The trial’s principal investigator, Bambino Gesu Children’s Hospital, division of metabolism Professor Carlo Dionisi-Vici said, “Given the central role of glutathione in cellular redox balance and antioxidant defense systems, we are eager to explore whether a therapeutic that increases glutathione such as EPI-743 will provide clinical benefit.”
Improvement in visual function is the primary endpoint of the placebo-controlled study while secondary outcome measurements assess neurologic and neuromuscular function, glutathione biomarkers, quality of life, in addition to safety parameters.
The investigation is aimed at assessing the efficacy of EPI-743 in disorders of intermediary metabolism that also result in redox disturbances.
EPI-743 is an orally absorbed small molecule that readily crosses into the central nervous system. It works by targeting the enzyme NADPH quinone oxidoreductase 1 (NQO1). Its mode of action is to synchronize energy generation in mitochondria with the need to counter cellular redox stress
FDA approves UCLA IND application to commence embryonic stem cell-based trial
12 feb 2013
The USFDA has approved the investigator investigational new drug (IND) application of University of California, Los Angeles (UCLA), the clinical partner of Advanced Cell Technology (ACT), to commence a clinical trial using the human embryonic stem cells (hESCs)-derived cells to treat severe myopia.
Embryonic stem cell-based trial was designed to assess the hESC-derived ACT’s retinal pigment epithelial (RPE) cells in patients with severe myopia (nearsightedness).
ACT chairman and CEO Gary Rabin said, “We are pleased to be on track to broaden the scope of our RPE program with the initiation of the new Investigator IND.”
Human embryonic stem cells (hESCs) are pluripotent cells derived from the inner cell mass of the blastocyst. They have the ability to renew themselves and to differentiate into a variety of different cell types that are found in the body. Unlike somatic or ‘adult’ stem cells, hESCs proliferate indefinitely. This, together with their ability to differentiate into most adult cell types, has resulted in the preferred use of these cells for research and therapeutic applications, as they represent a potentially indefinite source of therapeutic cells. Any cell therapy derived from hESCs would be allogeneic by nature. Some current studies involve the potential therapeutic application of hESCs for spinal cord injury, age-related macular degeneration (AMD), cardiovascular diseases, and diabetes. Among the start up cell therapy companies, Geron and Advanced Cell Technologies have pioneered clinical trials using cells differentiated from hESCs.
Mafenide Acetate Topical Solution 5% Approved: February 12, 2013 – Par Pharmaceutical, Inc. Sulfamylon
Mafenide acetate, USP is a synthetic antimicrobial agent designated chemically as a-amino-p- toluenesulfonamide monoacetate. It has the following structural formula:
 |
C7H10N2O2S • C2H4O2
M.W. 246.29Mafenide acetate, USP is a white, crystalline powder which is freely soluble in water.
SULFAMYLON® (mafenide acetate) For 5% Topical Solution is provided in packets containing 50 g of sterile mafenide acetate to be reconstituted in 1000 mL of Sterile Water for irrigation, USP or 0.9% Sodium Chloride Irrigation, USP. After mixing, the solution contains 5% w/v of mafenide acetate. The solution is an antimicrobial preparation suitable for topical administration. The solution Is not for Injection. The reconstituted solution may be held up to 28 days after preparation if stored in unopened containers. ONCE A CONTAINER IS OPENED, ANY UNUSED PORTION SHOULD BE DISCARDED AFTER 48 HOURS. Store the reconstituted solution at 20° to 25°C (68° to 77°F). Limited storage periods at 15° to 30°C (59° to 86°F) are acceptable.
- Mafenide Acetate Topical Solution 5%
Approved: February 12, 2013 – Par Pharmaceutical, Inc.
Generic for: Sulfamylon
FDA grants fresh approval for Novartis’ Zortress, Everolimus
dihydroxy-12-[(2R)-1-[(1S,3R,4R)-4-(2-hydroxyethoxy)-3-methoxycyclohexyl]propan-2-yl]-19,30-dimethoxy-15,17,21,23,29,35-hexamethyl-11,36-dioxa-4-azatricyclo[30.3.1.04,9]hexatriaconta-16,24,26,28-tetraene-2,3,10,14,20-pentone
Everolimus (RAD-001) is the 40-O-(2-hydroxyethyl) derivative of sirolimus and works similarly to sirolimus as an inhibitor of mammalian target of rapamycin (mTOR).
It is currently used as an immunosuppressant to prevent rejection of organ transplants and treatment of renal cell cancer and other tumours. Much research has also been conducted on everolimus and other mTOR inhibitors for use in a number of cancers.
It is marketed by Novartis under the tradenames Zortress (USA) and Certican (Europe and other countries) in transplantation medicine, and Afinitor in oncology.
18 feb 2013
The US Food and Drug Administration has approved Novartis’ Zortress for preventing organ rejection in adults receiving a liver transplant.
The Swiss major noted that Zortress (everolimus) is the first mammalian target of rapamycin (mTOR) inhibitor given the green light for use following liver transplantation and the first immunosuppressant approved by the FDA in over a decade for that use. The treatment is already on the market for preventing organ rejection in kidney transplant patients.
The approval was based on the largest liver transplant study to date, conducted in 719 liver transplant patients, Novartis says. The data showed that Zortress plus reduced-exposure tacrolimus (a well-established immunosuppresant) led to comparable efficacy and higher renal function compared to standard tacrolimus at 12 months.
Novartis Pharma chief David Epstein noted that this second indication for Zortress in just three years in the USA follows the recent European approval (in the fourth quarter of 2012) of the drug for liver transplants. It is marketed there as Certican and is also approved in Europe in kidney and heart transplantation.
Everolimus is also sold as Afinitor and Volubia in various oncology indications and is licensed to Abbott Laboratories (and sublicensed to Boston Scientific) for use in drug-eluting stents.
http://www.nature.com/nrd/journal/v8/n7/full/nrd2924.html
take a tour
Eritrea, africa
Eritrea – Wikipedia, the free encyclopedia
Eritrea (/ˌɛrɨˈtreɪ.ə/ or /ˌɛrɨˈtriːə/; Tigrinya: ኤርትራ ʾErtrā ; Arabic: إرتريا … Its name Eritrea is based on the Greek name for the Red Sea (Ἐρυθρὰ …
Isaias AfwerkiIsaias Afwerki (sometimes spelled Afewerki; Tigrinya: ኢሳይያስ …
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History of EritreaHistory of Eritrea. Coat of Arms of Eritrea. Pre-colonial. Kingdom …
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asmara
asmara
Massawa Old City
Eritrea – Island of the Red Seo of Eritrea –
keren
“Asara” traditional sesami oil press – Eritrea (Saied Ibrahim Yehdego)
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Nanyang Technological University, Singapore, prepares for trial of glaucoma drug
If glaucoma is left untreated, it can lead to blindness.–Courtesy of NIH
LipoLat, a controlled-release glaucoma therapeutic, is a suspension of nanocapsules each trapping a payload of drug. Designed as an injection into the conjunctiva (the outer layer of the eye), LipoLat gradually released the drug and was as effective as eye drops for as long as three months in preclinical trials. According to the researchers, this is now ready to move into human studies.
12th feb 2013
preclinical trials
http://media.ntu.edu.sg/NewsReleases/Pages/newsdetail.aspx?news=15fdbb3e-6724-4bc9-a699-a486c25f510e
For glaucoma patients, taking daily medication will soon become a thing of the past. With Nanyang Technological University’s (NTU) newest solution, a simple, quick and painless injection four times a year would be enough. The solution contains an anti-glaucoma drug wrapped in nano-sized capsules, and is delivered by an injection into the outer layer in the front of the eye (conjunctiva) by the doctor.
The nanocarrier will then slowly release the drug over several weeks. LipoLat, as it is known, is now ready for clinical trials. Extensive pre-clinical studies have shown that this single injection is as effective at treating glaucoma as taking daily eye drops for up to three months.
The newly launched Ocular Therapeutic Engineering Centre will work on this research. Housed at NTU’s School of Materials Science and Engineering, the center builds upon the School’s successful research collaboration with the Singapore Eye Research Institute. The center’s director Professor Subbu Venkatraman, who is also the school chair, said the center will build on the strong research collaboration between clinical scientists and NTU technologists, to develop new drug delivery systems for the eye.
“I hope to showcase this as a good example of how close interactions between medical practitioners and technology providers can lead to rapid translation of ideas to the clinic, such as LipoLat,” said Prof Venkatraman. “We are confident that the products co-developed at the centre will lead on to further discoveries and innovations in ocular therapy.” Working closely with Prof Venkatraman as the co-director of the center is Dr Tina Wong, an adjunct associate professor at the School of Materials Science and Engineering and a senior consultant at the Singapore National Eye Centre. She is also head of the Ocular Therapeutics and Drug Delivery Research Group at the Singapore Eye Research Institute
.
Extensive pre-clinical studies have shown that a single injection of the solution developed by Nanyang Technological University is effective in treating glaucoma
The solution developed by the university contains an anti-glaucoma drug wrapped in nano-sized capsules
The solution developed by the university contains an anti-glaucoma drug wrapped in nano-sized capsules
Working closely with Prof Venkatraman (picture) as the Co-Director of the centre is Dr Tina Wong (picture)
Celgene gains SFDA China, approval for marketing Revlimid (lenalidomide) to treat multiple myeloma
(RS)-3-(4-amino-1-oxo 1,3-dihydro-2H-isoindol- 2-yl)piperidine-2,6-dione
Lenalidomide
REVLIMID® is an oral immunomodulatory drug marketed in the United States and many international markets, in combination with dexamethasone, for treatment of patients with multiple myeloma who have received at least one prior therapy. It is also marketed in the United States and certain international markets for the treatment of transfusion-dependent anemia due to low- or intermediate-1-risk myelodysplastic syndromes, or MDS, associated with a deletion 5q cytogenetic abnormality with or without additional cytogenetic abnormalitie.Revlimid Worldwide annual sales in 2011 was $3.2bLenalidomide (Revlimid) is a derivative of thalidomideintroduced in 2004.It was initially intended as a treatment for multiple myeloma, for which thalidomide is an accepted therapeutic treatment. Lenalidomide has also shown efficacy in the class of hematological disorders known as myelodysplastic syndromes (MDS). Lenalidomide has significantly improved overall survival in myeloma (which generally carries a poor prognosis), although toxicity remains an issue for users. [1]It costs $163,381 per year for the average patient.[2]
Mechanism of action
Lenalidomide has been used to successfully treat both inflammatory disorders and cancers in the past 10 years. There are multiple mechanisms of action, and they can be simplified by organizing them as mechanisms of action in vitro and in vivo.[3] In vitro, lenalidomide has three main activities: direct anti-tumor effect, inhibition of the microenvironment support for tumor cells, and immunomodulatory role. In vivo, lenalidomide induces tumor cell apoptosis directly and indirectly by inhibition of bone marrow stromal cell support, by anti-angiogenic and anti-osteoclastogenic effects, and by immunomodulatory activity. Lenalidomide has a broad range of activities that can be exploited to treat many hematologic and solid cancers.
- McCarthy; Philip L. McCarthy, Kouros Owzar, Craig C. Hofmeister, et al. (May 10, 2012). “Lenalidomide after Stem-Cell Transplantation for Multiple Myeloma”. N Engl J Med 366 (19): 1770–1781. doi:10.1056/NEJMoa1114083. PMID 22571201.
- Badros, Ashraf Z. Badros (May 10, 2012). “Lenalidomide in Myeloma — A High-Maintenance Friend”. N Engl J Med 366 (19): 1836–1838. doi:10.1056/NEJMe1202819. PMID 22571206.
- Vallet S, Palumbo A, Raje N, Boccadoro M, Anderson KC (July 2008). “Thalidomide and lenalidomide: Mechanism-based potential drug combinations”. Leukemia & Lymphoma 49 (7): 1238–45. doi:10.1080/10428190802005191. PMID 18452080.
Peregrine Pharmaceuticals Announces Results From Phase II Clinical Trial of Bavituximab in Stage IV Pancreatic Cancer
TUSTIN, CA 02/13/13 — Peregrine Pharmaceuticals announced results from its 70 patient open-label, randomized Phase II clinical trial of bavituximab used in combination with gemcitabine in patients with previously untreated, advanced Stage IV pancreatic cancer. The trial included the enrollment of patients with advanced metastatic disease including significant liver involvement and poor performance status associated with rapid disease progression. Results showed that the combination of bavituximab and gemcitabine resulted in more than a doubling of overall response rates (ORR) and an improvement in overall survival (OS) when compared with gemcitabine alone (control arm). In the trial, patients treated with a combination of bavituximab and gemcitabine had a 28% tumor response rate as compared to 13% in the control arm. Median OS, the primary endpoint of the trial, was 5.6 months for the bavituximab plus gemcitabine arm and 5.2 months for the control arm (hazard ratio = 0.75).
Bavituximab binds to phosphatidylserine which is exposed on the surface of certain atypical animal cells, including tumour cells and cells infected with any of six different families of virus. These viral families contain the viruses hepatitis C, influenza A and B, HIV 1 and 2, measles, respiratory syncytial virus and pichinde virus, which is a model for the deadly Lassa virus.[2] Other cells are not affected since phosphatidylserine normally is only intracellular.[3]
Bavituximab binds to various aminophospholipids and is dependent on interaction with plasma protein beta-2 glycoprotein I to mediate binding.
These target aminophospholipids, usually residing only on the inner leaflet of the plasma membrane of cells, become exposed in virally infected, damaged or malignant cells, and more generally in most cells undergoing the process of apoptosis.
The antibody’s binding to phospholipids alerts the body’s immune system to attack the tumor endothelial cells, thrombosing the tumor’s vascular network and/or attacking free floating virally infected and metastatic cells while potentially minimizing side effects in healthy tissues.
- Statement on a nonproprietary name adopted by the USAN council
- Nature Medicine 14, 1357 – 1362 (2008)
- He, J.; Yin, Y.; Luster, T. A.; Watkins, L.; Thorpe, P. E. (2009). “Antiphosphatidylserine Antibody Combined with Irradiation Damages Tumor Blood Vessels and Induces Tumor Immunity in a Rat Model of Glioblastoma”. Clinical Cancer Research 15 (22): 6871–6880. doi:10.1158/1078-0432.CCR-09-1499. PMID 19887482. edit
- New Progression-Free Survival Data From Peregrine’s Bavituximab in Phase II Refractory Breast Cancer
- Phase II Advanced Breast Cancer Data to Be Presented at ASCO Highlight Promising Tumor Response and Progression-Free Survival Data With Peregrine’s Bavituximab
- Pharma company completes humanization of 3G4 antibody
- He, J.; Luster, T. A.; Thorpe, P. E. (2007). “Radiation-Enhanced Vascular Targeting of Human Lung Cancers in Mice with a Monoclonal Antibody That Binds Anionic Phospholipids”. Clinical Cancer Research 13 (17): 5211–5218. doi:10.1158/1078-0432.CCR-07-0793. PMID 17785577. edit
- Ran; Downes, A.; Thorpe, P. E. (2002). “Increased exposure of anionic phospholipids on the surface of tumor blood vessels”. Cancer Research 62 (21): 6132–6140. PMID 12414638.
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New Drug Approvals 