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DRUG APPROVALS BY DR ANTHONY MELVIN CRASTO
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Phase 3 Amicus in collaboration with GlaxoSmithKline (GSK) is developing the investigational pharmacological chaperone migalastat HCl for the treatment of Fabry disease
CAS Number:75172-81-5-
3,4,5-Piperidinetriol,2-(hydroxymethyl)-, hydrochloride (1:1), (2R,3S,4R,5S)-
- Molecular Structure:
- Formula:C6H14ClNO4
- Molecular Weight:199.63
- Synonyms:3,4,5-Piperidinetriol,2-(hydroxymethyl)-, hydrochloride, (2R,3S,4R,5S)- (9CI);3,4,5-Piperidinetriol,2-(hydroxymethyl)-, hydrochloride, [2R-(2a,3a,4a,5b)]-;Migalastat hydrochloride;Galactostatin hydrochloride;(2S,3R,4S,5S)-2-(hydroxymethyl)piperidine-3,4,5-triol hydrochloride;
- Melting Point:260 °C
- Boiling Point:382.7 °C at 760 mmHg
- Flash Point:185.2 °C
end feb 2013
About Amicus Therapeutics
Amicus Therapeutics is a biopharmaceutical company at the forefront of therapies for rare and orphan diseases. The Company is developing orally-administered, small molecule drugs called pharmacological chaperones, a novel, first-in-class approach to treating a broad range of human genetic diseases. Amicus’ late-stage programs for lysosomal storage disorders include migalastat HCl monotherapy in Phase 3 for Fabry disease; migalastat HCl co-administered with enzyme replacement therapy (ERT) in Phase 2 for Fabry disease; and AT2220 co-administered with ERT in Phase 2 for Pompe disease.
About Migalastat HCl
Amicus in collaboration with GlaxoSmithKline (GSK) is developing the investigational pharmacological chaperone migalastat HCl for the treatment of Fabry disease. Amicus has commercial rights to all Fabry products in the United States and GSK has commercial rights to all of these products in the rest of world.
As a monotherapy, migalastat HCl is designed to bind to and stabilize, or “chaperone” a patient’s own alpha-galactosidase A (alpha-Gal A) enzyme in patients with genetic mutations that are amenable to this chaperone in a cell-based assay. Migalastat HCl monotherapy is in Phase 3 development (Study 011 and Study 012) for Fabry patients with genetic mutations that are amenable to this chaperone monotherapy in a cell-based assay. Study 011 is a placebo-controlled study intended primarily to support U.S. registration, and Study 012 compares migalastat HCl to ERT to primarily support global registration.
For patients currently receiving ERT for Fabry disease, migalastat HCl in combination with ERT may improve ERT outcomes by keeping the infused alpha-Gal A enzyme in its properly folded and active form thereby allowing more active enzyme to reach tissues.2 Migalastat HCl co-administered with ERT is in Phase 2 (Study 013) and migalastat HCl co-formulated with JCR Pharmaceutical Co. Ltd’s proprietary investigational ERT (JR-051, recombinant human alpha-Gal A enzyme) is in preclinical development.
About Fabry Disease
Fabry disease is an inherited lysosomal storage disorder caused by deficiency of an enzyme called alpha-galactosidase A (alpha-Gal A). The role of alpha-Gal A within the body is to break down specific lipids in lysosomes, including globotriaosylceramide (GL-3, also known as Gb3). Lipids that can be degraded by the action of α-Gal are called “substrates” of the enzyme. Reduced or absent levels of alpha-Gal A activity leads to the accumulation of GL-3 in the affected tissues, including the kidneys, heart, central nervous system, and skin. This accumulation of GL-3 is believed to cause the various symptoms of Fabry disease, including pain, kidney failure, and increased risk of heart attack and stroke.
It is currently estimated that Fabry disease affects approximately 5,000 to 10,000 people worldwide. However, several literature reports suggest that Fabry disease may be significantly under diagnosed, and the prevalence of the disease may be much higher.
2. Benjamin, et al., Molecular Therapy: April 2012, Vol. 20, No. 4, pp. 717–726.
http://clinicaltrials.gov/show/NCT01458119
http://www.docstoc.com/docs/129812511/migalastat-hcl
| Chemical Name: | DEOXYGALACTONOJIRIMYCIN, HYDROCHLORIDE |
| Synonyms: | DGJ;Amigal;Unii-cly7m0xd20;GALACTOSTATIN HCL;DGJ, HYDROCHLORIDE;Migalastat hydrochloride;Galactostatin hydrochloride;DEOXYGALACTONOJIRIMYCIN HCL;1-DEOXYGALACTONOJIRIMYCIN HCL;1,5-dideoxy-1,5-imino-d-galactitol |
Lumacaftor, VX-809 an experimental drug for the treatment of Late-Stage cystic fibrosis, being developed by Vertex Pharmaceuticals
3-{6-{[1-(2,2-difluoro-1,3-benzodioxol-5-yl)cyclopropanecarbonyl]amino}-3-methylpyridin-2-yl}benzoic acid
26,FEB 2013
syn at >>>>>>>https://newdrugapprovals.org/2013/07/28/3274/
Vertex Pharmaceuticals announced Tuesday night the design of two phase III studies for its combination therapy to treat the most common form of cystic fibrosis. The studies will each run for six months, so results could be ready as early as the end of 2013 or during first half of 2014.
The studies announced Tuesday will evaluate the two different doses of an experimental medicine VX-809 in combination with Kalydeco. Each study will enroll 500 cystic fibrosis patients randomized to either the VX-809/Kalydeco arms or a placebo for six months of treatment. The studies’ primary endpoint will be the relative improvement in lung function of VX-809/Kalydeco compared to placebo.
Last fall, Vertex presented data from a phase II study demonstrating that a 600 mg dose of VX-809 and Kalydeco worked synergistically to improve lung function in cystic fibrosis patients with the F508del mutation compared to placebo. This same dose combination will be tested in the phase III study along with a higher 800 mg (actually, 400 mg given twice a day) dose of VX-809 plus Kalydeco.
Vertex also announced new data from this phase II study on Tuesday night showing similar lung function improvements between the 800 mg and 600 mg doses of VX-809. For this reason, the higher dose was included in the phase III studies.
Along with the two phase III studies in adult patients, Vertex will also conduct a six-month study of the combination therapy in pediatric patients ages 6 to 11. This study, along with the data from the adult studies, may be used to expand the combination therapy’s approval into younger patients.
In January, FDA anointed Kalydeco and VX-809 with Breakthrough Therapy Designation as part of the agency’s efforts to accelerate the development and approval of drugs for serious and life-threatening disease. Vertex did not say whether Breakthrough Designation played a specific role in the VX-809/Kalydeco phase III program but the relatively short six-month duration of the studies plus the ability to test the combination in children at the same time does accelerate the development of the combination therapy. If the data from the studies are positive, the drugs could be approved sooner than expected and for more patients.
Lumacaftor (USAN, codenamed VX-809) is an experimental drug for the treatment of cystic fibrosis, being developed by Vertex Pharmaceuticals. The drug is designed to be effective in patients that have the F508del mutation in the cystic fibrosis transmembrane conductance regulator (CFTR), the defective protein that causes the disease. F508del, meaning that the amino acid phenylalanine in position 508 is missing, is found in about 60% of cystic fibrosis patients.[1]
Interim results from a Phase II clinical trial indicate that patients with the most common form of genetic mutation causing cystic fibrosis homozygous F508del had an 8.5% increase in lung function (FEV1) after 56 days on a combination of lumacaftor and ivacaftor (Kalydeco).[2]
- Merk; Schubert-Zsilavecz. (in German)Pharmazeutische Zeitung 156 (37): 24–27.
- Vertex Pharmaceuticals. May 29,2012.
- syn at >>>>>>>https://newdrugapprovals.org/2013/07/28/3274/
- syn at >>>>>>>https://newdrugapprovals.org/2013/07/28/3274/
Pernix Therapeutics Holdings, Inc., a specialty pharmaceutical company, today announced that its subsidiary, Hawthorn Pharmaceuticals, Inc., has received FDA approval of a NDA for Vituz Oral Solution (hydrocodone bitartrate and chlorpheniramine maleate).
Hydrocodone bitartrate is morphinan-6-one, 4,5-epoxy-3-methoxy-17-methyl-, (5α)-, [R-(R*,R*)]-2,3-dihydroxybutanedioate (1:1), hydrate (2:5); also known as 4,5α-Epoxy-3-methoxy-17-methylmorphinan-6-one tartrate (1:1) hydrate (2:5); a fine white crystal or crystalline powder, which is derived from the opium alkaloid, thebaine; and may be represented by the following structural formula:
 |
Hydrocodone Bitartrate
C18H21N03•C4H606•2.5 H20
Molecular weight = 494.5
Chlorpheniramine maleate is 2-pyridinepropanamine, γ-(4-chlorophenyl)-N,N-dimethyl-, (Z)-2-butenedioate (1:1) and has the following chemical structure:
 |
Chlorpheniramine Maleate
C16H19C1N2•C4H404
Molecular weight = 390.86
Feb 28, 2013 – Pernix Therapeutics Holdings, Inc., a specialty pharmaceutical company, today announced that its subsidiary, Hawthorn Pharmaceuticals, Inc., has received U.S. Food and Drug Administration (FDA) approval of a new drug application (NDA) for Vituz Oral Solution (hydrocodone bitartrate and chlorpheniramine maleate). Vituz is indicated for the relief of cough and symptoms associated with upper respiratory allergies or a common cold in adults 18 years of age and older.
Cooper Collins, President and CEO of Pernix, said, “Vituz broadens our cough and cold product line and is our first NDA approved by the FDA, since we closed the acquisition of Hawthorn and Cypress at the end of December 2012. We look forward to the launch of this new treatment option for cough and cold symptoms, which is expected prior to the fall of this year.”
FDA Approves Osphena,Ospemifene for Postmenopausal Women Experiencing Dyspareunia
Ospemifene
CAS Number: 128607-22-7
Molecular Formula: C24H23ClO2
Molecular Weight: 378.89 g.mol-1
February 26, 2013 — The U.S. Food and Drug Administration today approved Osphena (ospemifene) to treat women experiencing moderate to severe dyspareunia (pain during sexual intercourse), a symptom of vulvar and vaginal atrophy due to menopause.
Dyspareunia is a condition associated with declining levels of estrogen hormones during menopause. Less estrogen can make vaginal tissues thinner, drier and more fragile, resulting in pain during sexual intercourse.
Osphena, a pill taken with food once daily, acts like estrogen on vaginal tissues to make them thicker and less fragile, resulting in a reduction in the amount of pain women experience with sexual intercourse.
“Dyspareunia is among the problems most frequently reported by postmenopausal women,” said Victoria Kusiak, M.D., deputy director of the Office of Drug Evaluation III in the FDA’s Center for Drug Evaluation and Research. “Osphena provides an additional treatment option for women seeking relief.”
Osphena’s safety and effectiveness were established in three clinical studies of 1,889 postmenopausal women with symptoms of vulvar and vaginal atrophy. Women were randomly assigned to receive Osphena or a placebo. After 12 weeks of treatment, results from the first two trials showed a statistically significant improvement of dyspareunia in Osphena-treated women compared with women receiving placebo. Results from the third study support Osphena’s long-term safety in treating dyspareunia.
Common side effects reported during clinical trials included hot flush/flashes, vaginal discharge, muscle spasms, genital discharge and excessive sweating.
Osphena is marketed by Florham Park, N.J.-based Shionogi, Inc.
- Shionogi Files a New Drug Application for Ospemifene Oral Tablets 60mg for the Treatment of Vulvar and Vaginal Atrophy – May 9, 2012
FDA Approves Stivarga, Regorafenib for Advanced Gastrointestinal Stromal Tumors
Regorafenib
cas 755037-03-7
4-[4-({[4-Chloro-3-(trifluoromethyl)phenyl]carbamoyl}amino)-3-fluorophenoxy]-N-methylpyridine-2-carboxamide hydrate
February 25, 2013 — The U.S. Food and Drug Administration today expanded the approved use of Stivarga (regorafenib) to treat patients with advanced gastrointestinal stromal tumors (GIST) that cannot be surgically removed and no longer respond to other FDA-approved treatments for this disease.
GIST is a tumor in which cancerous cells form in the tissues of the gastrointestinal tract, part of the body’s digestive system. According to the National Cancer Institute, an estimated 3,300 to 6,000 new cases of GIST occur yearly in the United States, most often in older adults.
Stivarga, a multi-kinase inhibitor, blocks several enzymes that promote cancer growth. With this new approval, Stivarga is intended to be used in patients whose GIST cancer cannot be removed by surgery or has spread to other parts of the body (metastatic) and is no longer responding to Gleevec (imatinib) and Sutent (sunitinib), two other FDA-approved drugs to treat GIST.
“Stivarga is the third drug approved by the FDA to treat gastrointestinal stromal tumors,” said Richard Pazdur, M.D., director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research. “It provides an important new treatment option for patients with GIST in which other approved drugs are no longer effective.”
Stivarga was approved in September 2012 to treat colorectal cancer. It is marketed by Bayer HealthCare Pharmaceuticals, based in Wayne, N.J. Gleevec is marketed by East Hanover, N.J.-based Novartis, and Sutent is marketed by New York City-based Pfizer.
Regorafenib (BAY 73-4506, commercial name Stivarga) is an oral multi-kinase inhibitor developed by Bayer which targets angiogenic, stromal and oncogenic receptor tyrosine kinase (RTK). Regorafenib shows anti-angiogenic activity due to its dual targetedVEGFR2-TIE2 tyrosine kinase inhibition. It is currently being studied as a potential treatment option in multiple tumor types.[1]
Metastatic colorectal cancer
Regorafenib demonstrated to increase the overall survival of patients with metastaticcolorectal cancer[2] and has been approved by the US FDA on September 27, 2012.[3]Stivarga is being approved with a Boxed Warning alerting patients and health care professionals that severe and fatal liver toxicity occurred in patients treated with Stivarga during clinical studies. The most common side effects reported in patients treated with Stivarga include weakness or fatigue, loss of appetite, hand-foot syndrome (also called palmar-plantar erythrodysesthesia), diarrhea, mouth sores (mucositis), weight loss, infection, high blood pressure, and changes in voice volume or quality (dysphonia).[4]
- “Bayer Announces New Data on Oncology Portfolio To Be Presented at the ECCO-ESMO Congress 2009”. Retrieved 2009-09-19.
- “Phase III Trial of Regorafenib in Metastatic Colorectal Cancer Meets Primary Endpoint of Improving Overall Survival”. Retrieved 2011-10-26.
- “FDA approves new treatment for advanced colorectal cancer”. 27 Sep 2012.
- “FDA Prescribing Information”. 27 Sept 2012.
Medical Imaging Drugs Advisory Committee Recommends Approval of Guerbet NDA for Dotarem (gadoterate meglumine)
| Cas No. | 98059-18-8 |
| Name | 2-[4,7-bis(carboxylatomethyl)-10-(carboxymethyl)-1,4,7, 10-tetrazacyclododec-1-yl]acetate; gadolinium(3+); (2R,3R,4R,5S)-6-(methylamino)hexane-1,2,3,4,5-pentol |
Dotarem (gadoterate meglumine)
Company: Guerbet
Treatment for: Diagnostic
Dotarem (gadoterate meglumine) is a gadolinium-based contrast agent under review for use in magnetic resonance imaging (MRI).
VILLEPINTE, France, Feb. 14, 2013 Guerbet, the contrast agent specialist for medical imaging, today announced that the Medical Imaging Drugs Advisory Committee to US Food and Drug Administration (FDA) has voted unanimously by votes of 17 to 0 to recommend that FDA approve the New Drug Application (NDA) for Dotarem (gadoterate meglumine) for adults, and for pediatric use for children two years of age and older. The Committee voted 10 to 6 (with one member abstaining) not to recommend at this time approval of the indication for children under two years of age.
Dotarem is the only macrocyclic and ionic gadolinium-based contrast agent (GBCA) for the intravenous use with magnetic resonance imaging (MRI) in the brain (intracranial), spine and associated tissues in adults and pediatric patients to detect and visualize areas with disruption of the blood-brain barrier (BBB) and/or abnormal vascularity. The Guerbet NDA recommended dose is 0.1 mmol Gd/kg.
Gadoteric acid
Gadoteric acid (trade names Artirem, Dotarem) is a macrocycle-structured gadolinium-based MRI contrast agent. It consists of the organic acid DOTA as a chelating agent, and gadolinium (Gd3+), and is used in form of the meglumine salt.[1] The drug is approved and used in a number of countries worldwide.[2]
References
- Herborn, C. U.; Honold, E.; Wolf, M.; Kemper, J.; Kinner, S.; Adam, G.; Barkhausen, J. (2007). “Clinical Safety and Diagnostic Value of the Gadolinium Chelate Gadoterate Meglumine (Gd-DOTA)”. Investigative Radiology 42 (1): 58–62. doi:10.1097/01.rli.0000248893.01067.e5. PMID 17213750. edit
- Drugs.com: Gadoteric Acid
A gadolinium chelate paramagnetic contrast agent. When placed in a magnetic field, gadoterate meglumine produces a large magnetic moment and so a large local magnetic field, which can enhance the relaxation rate of nearby protons; as a result, the signal intensity of tissue images observed with magnetic resonance imaging (MRI) may be enhanced. Because this agent is preferentially taken up by normal functioning hepatocytes, normal hepatic tissue is enhanced with MRI while tumor tissue is unenhanced. In addition, because gadobenate dimeglumine is excreted in the bile, it may be used to visualize the biliary system using MRI.
FDA approves Kadcyla (ado-trastuzumab emtansine), a new therapy for patients with HER2-positive, late-stage (metastatic) breast cancer.
Structure of trastuzumab emtansine. An ADC is a three-block “engine” — antibody-linker-drug — and each part of the composite molecule has to be carefully selected and assembled. Considered as an armed-antibody, an ADC is a bi-dentate construction where both parts (antibody and drug) of the molecule combine their effect to ensure selectivity and potency. The role of the linker arm is of paramount importance demanding a fine tuning to execute the controlled release and delivery of the two active components in the tumor environment.
Feb. 22, 2013
FDA approves new treatment for late-stage breast cancer
The U.S. Food and Drug Administration today approved Kadcyla (ado-trastuzumab emtansine), a new therapy for patients with HER2-positive, late-stage (metastatic) breast cancer.
HER2 is a protein involved in normal cell growth. It is found in increased amounts on some types of cancer cells (HER2-positive), including some breast cancers. In these HER2-positive breast cancers, the increased amount of the HER2 protein contributes to cancer cell growth and survival.
Kadcyla is intended for patients who were previously treated with trastuzumab, another anti-HER2 therapy, and taxanes, a class of chemotherapy drugs commonly used for the treatment of breast cancer.
“Kadcyla is trastuzumab connected to a drug called DM1 that interferes with cancer cell growth,” said Richard Pazdur, M.D., director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research. “Kadcyla delivers the drug to the cancer site to shrink the tumor, slow disease progression and prolong survival. It is the fourth approved drug that targets the HER2 protein.”
Referred to as T-DM1 during clinical research, Kadcyla was reviewed under the FDA’s priority review program, which provides for an expedited six-month review of drugs that may provide safe and effective therapy when no satisfactory alternative therapy exists, or offer significant improvement compared to marketed products. Other FDA-approved drugs used to treat HER2-positive breast cancer include trastuzumab (1998), lapatinib (2007) and pertuzumab (2012).
Kadcyla, trastuzumab and pertuzumab are marketed by South San Francisco, Calif.-based Genentech, a member of the Roche Group. Lapatinib is marketed by GlaxoSmithKline, based in Research Triangle Park, N.C
ImmunoGen, Inc. a biotechnology company that develops anticancer therapeutics using its TAP technology, today announced that Roche has reported that the U.S. Food and Drug Administration (FDA) has granted marketing approval to Kadcyla for the treatment of people with HER2-positive metastatic breast cancer who have received prior treatment with Herceptin® (trastuzumab) and a taxane chemotherapy.
“This is a big day for the patients with this cancer and for ImmunoGen,” commented Daniel Junius, President and CEO. “In clinical testing, the findings with Kadcyla in this patient population have been impressive, and we’re delighted the product can now be used by practicing oncologists across the US. In addition to its importance from a medical perspective, commercialization of Kadcyla also marks the start of ImmunoGen earning royalty income.”
Mr. Junius continued, “The efficacy and tolerability seen with Kadcyla underscores the transformative potential of our technology. Kadcyla is the most advanced of ten compounds with our TAP technology already in the clinic, with more in earlier stages of development. We are hopeful that in the future many different types of cancers will be routinely treated with TAP compounds.”
Genentech licensed from ImmunoGen exclusive rights to use the Company’s maytansinoid TAP technology to develop anticancer products targeting HER2.
According to Genentech, Kadcyla will cost $9,800 per month, compared to $4,500 per month for regular Herceptin. The company estimates a full course of Kadcyla, about nine months of medicine, will cost $94,000. Thus, the cost of the drug is beyond the reach of many women unless they have an insurance plan.
”””””’
Afatinib
-
- Synonyms:BIBW 2992
- ATC:L01XE13
- Use:anticancer; tyrosine kinase inhibitor
- Chemical name:N-[4-[(3-chloro-4-fluorophenyl)amino]-7-[[(3S)-tetrahydro-3-furanyl]oxy]-6-quinazolinyl]-4-(dimethylamino)-2-butenamide; N-[(3-chloro-4-fluorophenyl)amino]-6-{[4-(N,N-dimethylamino)-1-oxo-2-buten-1-yl]amino}-7-((S)-tetrahydrofuran-3-yloxy)-quinazoline
- Formula:C24H25ClFN5O3
- MW:485.9 g/mol
- CAS-RN:439081-18-2; 850140-72-6
Derivatives
dimaleate
- Formula:C32H33ClFN5O11
- MW:718.1 g/mol
- CAS-RN:850140-73-7
Substance Classes
Synthesis Path
Substances Referenced in Synthesis Path
| CAS-RN | Formula | Chemical Name | CAS Index Name |
|---|---|---|---|
| 446-32-2 | C7H6FNO2 | 4-fluoro-anthranilic acid | |
| 162012-70-6 | C8H3ClFN3O2 | 4-chloro-7-fluoro-6-nitroquinazoline | |
| 367-21-5 | C6H5ClFN | 3-chloro-4-fluoroaniline | |
| 86087-23-2 | C4H8O2 | (S)-(+)-3-hydroxytetrahydrofuran | |
| 314771-76-1 | C18H16ClFN4O2 | N-(3-chloro-4-fluorophenyl)-7-((tetrahydrofuran-3-yl)oxy)quinazoline-4,6-diamine | |
| 13991-36-1 | C4H5BrO2 | bromocrotonic acid | |
| 3095-95-2 | C6H13O5P | diethylphophonoacetic acid | |
| 618061-76-0 | C24H27ClFN4O6P | Diethyl-{[4-((3-chloro-4-fluorophenyl)amino)-7-(((S)-tetrahydro- furan-3-yloxy)quinazolin-6-yl)carbamoyl]-methyl}phosphonate |
|
| 3616-56-6 | C8H19NO2 | (dimethylamino)-acetaldehyde diethylacetate |
Trade Names
| Country | Trade Name | Vendor | Annotation |
|---|---|---|---|
| USA | Gilotrif | Boehringer Ingelheim, 2013 | |
| EU | Giotrif | Boehringer Ingelheim, 2013 |
Formulations
- tabs.; 20, 30 and 40 mg
References
-
- a US 6 251 912 (American Cyanamid; 26.6.2001; appl. 29.7.1998; USA-prior. 1.8.1997).
- WO 0 250 043 (Boehringer Ingelheim; 27.6.2002; appl. 12.12.2001; DE-prior. 20.12.2000).
- US RE 43431 (Boehringer Ingelheim; 29.5.2012; appl. 18.8.2009; DE-prior. 20.12.2000).
- b US 8 426 586 (Boehringer Ingelheim; 1.2.2007; appl. 14.7.2006; DE-prior. 17.10.2003).
-
crystalline forms of Afatinib di-maleate:
- Solca, F. et al., J. Pharmacol. Exp. Ther., (2012) 343(2), 342-350.
- WO 2013 052157 (Ratiopharm/Teva; 11.4.2013; appl. 25.4.2012; USA-prior. 6.10.2011).
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.
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
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:
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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
New Drug Approvals 