FLAGS AND HITS
DRUG APPROVALS BY DR ANTHONY MELVIN CRASTO
FACEBOOK
...................................................................Join me on twitter
..................................................................Join me on google plus
GoogleplusMYSELF
USFDA Approves first systemic antisense drug Kynamro (mipomersen sodium) Injection for treatment of Homozygous Familial Hyperholesterolemia
G*-C*-C*-U*-C*-dA-dG-dT-dC-dT-dG-dmC-dT-dT-dmC-G*-C*-A*-C*-C*[d= 2′-deoxy,*= 2′-O-(2-methoxyethyl)]
with 3’→5′ phosphorothioate linkages
cas no 629167-92-6
USFDA Approves first systemic antisense drug Kynamro (mipomersen sodium) Injection for treatment of Homozygous Familial Hyperholesterolemia
30 January 2013
Sanofi and its subsidiary Genzyme, and Isis Pharmaceuticals Inc today announced that the U.S. Food and Drug Administration (FDA) has approved its New Drug Application (NDA) for KYNAMRO(mipomersen sodium) injection. KYNAMRO, given as a 200 mg weekly subcutaneous injection, has been approved as an adjunct to lipid-lowering medications and diet to reduce low density lipoprotein-cholesterol (LDL-C), apolipoprotein B (Apo B), total cholesterol (TC), and non-high density lipoprotein-cholesterol (non HDL-C) in patients with homozygous familial hypercholesterolemia.
In the United States, HoFH, an orphan indication, occurs in approximately one in one million individuals. For those with HoFH, heart attacks and death often occur before age 30.
Mipomersen (previously ISIS 301012, trade name Kynamro) is a cholesterol-reducing drug candidate. It is an antisense therapeutic that targets the messenger RNA forapolipoprotein B.[1][2][3] It is administered as a weekly injection.Structure
The compound is a ‘second-generation’ antisense oligonucleotide; the nucleotides are linked with phosphorothioate linkages rather than the phosphodiester linkages of RNA andDNA, and the sugar parts are deoxyribose in the middle part of the molecule and 2′-O-methoxyethyl-modified ribose at the two ends. These modifications make the drug resistant to degradation by nucleases, allowing it to be administered weekly. The drug accumulates in the liver, which is convenient since apolipoprotein B predominantly acts there.
The complete sequence is
G*-C*-C*-U*-C*-dA-dG-dT-dC-dT-dG-dmC-dT-dT-dmC-G*-C*-A*-C*-C*[d= 2′-deoxy,*= 2′-O-(2-methoxyethyl)]
with 3’→5′ phosphorothioate linkages.[4]
- Merki E, Graham MJ, Mullick AE, et al. (August 2008). “Antisense oligonucleotide directed to human apolipoprotein B-100 reduces lipoprotein(a) levels and oxidized phospholipids on human apolipoprotein B-100 particles in lipoprotein(a) transgenic mice”.Circulation 118 (7): 743–53. doi:10.1161/CIRCULATIONAHA.108.786822. PMID 18663084.
- El Harchaoui K, Akdim F, Stroes ES, Trip MD, Kastelein JJ (2008). “Current and future pharmacologic options for the management of patients unable to achieve low-density lipoprotein-cholesterol goals with statins”. Am J Cardiovasc Drugs 8 (4): 233–42.doi:10.2165/00129784-200808040-00003. PMID 18690757.
- Athyros VG, Kakafika AI, Tziomalos K, Karagiannis A, Mikhailidis DP (July 2008). “Antisense technology for the prevention or the treatment of cardiovascular disease: the next blockbuster?”. Expert Opin Investig Drugs 17 (7): 969–72.doi:10.1517/13543784.17.7.969. PMID 18549334.
- Statement on a nonproprietary name adopted by the USAN council: Mipomersen sodium
FDA APPROVES BIOTESTS BIVIGAM TO TREAT PRIMARY HUMORAL IMMUNODEFIECIENCY
FDA APPROVES BIOTESTS BIVIGAM TO TREAT PRIMARY HUMORAL IMMUNODEFIECIENCY
Jan 31, 2013,
Biotest Pharmaceuticals Corporation (BPC), a wholly owned U.S. subsidiary of Biotest AG, recently announced the U.S. Food and Drug Administration’s (FDA) approval of BIVIGAM™, its new intravenous immune globulin, for the treatment of patients with Primary Humoral Immunodeficiency (PI).
BIVIGAM is the first new intravenous immune globulin (IVIG) to be approved by the FDA with a validated assay for measuring potential thrombogenic activity. Thrombin generation tests are utilized to detect procoagulant activity. BPC plans to begin shipments of the product shortly.
To reduce the risk of thromboembolic events that PI patients have experienced in the past with alternative products, BPC initiated the development and validation of a TGA test in close cooperation with the FDA. Every lot of BPC’s BIVIGAM will be screened before release to assure the product fulfills the stringent release criteria pertaining to the threshold levels of Factor XIa. Increased Factor XIa has been identified as one of the risk factors associated with thromboembolic events following immune globulin intravenous therapy.
BIVIGAM is a sugar-free, glycine stabilized intravenous immune globulin that was approved by the FDA on December 19, 2012 and is available in 50 mL (5 gram) and 100 mL (10 gram) tamper-evident vials. The product uses a label with an integrated hanger and the packaging material is latex free. It is manufactured in a state-of-the-art US facility and will be available exclusively for patients and healthcare professionals in the USA. For Full Prescribing Information and more information about the product, the indication and additional services, please visit www.BIVIGAM.com.
BIVIGAM is a purified, sterile, ready-to-use preparation of concentrated humanimmunoglobulin G (IgG) antibodies. The distribution of IgG subclasses is similar to that of normal plasma.19,20 The active ingredient is human immunoglobulin purified from source human plasma and processed using a modified classical Cohn Method 6 / Oncley Method 9 fractionation procedure. BIVIGAM contains 100 ± 10 mg/mL protein, of which not less than 96% is human immunoglobulin obtained from source human plasma. It is formulated in water for injection containing 0.100-0.140 M sodium chloride, 0.20-0.29 M glycine, 0.15–0.25% polysorbate 80, and pH 4.0–4.6. BIVIGAM contains ≤ 200 μg/mL of IgA.
Each plasma donation used for the manufacture of BIVIGAM is collected from FDA licensed facilities and undergoes rigorous testing. Plasma donations must test negative for hepatitis B virus (HBV) surface antigen (HBsAg), antibodies to human immunodeficiency virus (HIV) strains 1 and 2 (anti-HIV-½), and antibodies to the hepatitis C virus (anti-HCV) as determined by enzyme immuno assay (EIA). In addition, each plasma unit must test negative and/or non-reactive for HIV RNA, HCV RNA, HBV DNA, Hepatitis A Virus (HAV) RNA, and Parvovirus B19 (B19 virus) DNA as determined by Nucleic Acid Amplification Testing (NAT) of plasma minipools. NAT for B19 virus DNA is also performed on a sample of the manufacturing pool and the limit for B19 virus DNA in a manufacturing pool is set not to exceed 104 IU/mL.
The manufacturing process of BIVIGAM employs three steps to remove/inactivateadventitious viruses to minimize the risk of virus transmission. The steps are “Precipitation and removal of fraction III” during cold ethanol fractionation, classical “Solvent/detergent treatment” and “35 nm virus filtration”. In compliance with current guidelines, the steps have been separately validated in a series of in vitro experiments for their capacity to inactivate or remove both enveloped and non-enveloped viruses.
Precipitation and removal of fraction III removes both enveloped and non-enveloped viruses, solvent/detergent treatment represents a virus inactivation step for enveloped viruses, and 35 nm virus filtration removes both enveloped and non-enveloped viruses by size exclusion. In addition to the steps above, low pH during several steps of the production process contributes to virus inactivation. The results of virus validation studies for BIVIGAM are shown in Table 3, expressed as log10 reduction factors.
FDA Approves Ravicti (glycerol phenylbutyrate), feb 2013, for the Chronic Management of Some Urea Cycle Disorder
glycerol phenylbutyrate, 611168-24-2 cas no
FDA Approves Ravicti (glycerol phenylbutyrate)for the Chronic Management of Some Urea Cycle Disorders
Ravicti is marketed by Hyperion Therapeutics, based in South San Francisco, Calif.
February 1, 2013 — The U.S. Food and Drug Administration today approved Ravicti (glycerol phenylbutyrate) for the chronic management of some urea cycle disorders (UCDs) in patients ages 2 years and older.
UCDs are genetic disorders that involve deficiencies of specific enzymes involved in the urea cycle, a series of biochemical steps normally required to remove ammonia from the blood. When protein is absorbed and broken down by the body, it produces nitrogen as a waste product. The urea cycle removes nitrogen from the blood and converts it to urea, which is removed from the body through urine. In people with UCDs, nitrogen accumulates and remains in the body as ammonia, which can travel to the brain and cause brain damage, coma or death.
Ravicti, a liquid taken three times a day with meals, helps dispose of ammonia in the body. It is intended for patients whose UCD cannot be managed by a protein-restricted diet or amino acid supplements alone. Ravicti must be used with a protein-restricted diet and, in some cases, dietary supplements.
“Ravicti provides another treatment for chronic management of urea cycle disorders, a group of life-threatening conditions,” said Donna Griebel, M.D., director of the Division of Gastrointestinal and Inborn Errors Products in the FDA’s Center for Drug Evaluation and Research. “The approval of this new therapeutic option demonstrates FDA’s commitment to providing treatments for patients suffering from rare diseases.”
Ravicti was reviewed under the agency’s fast track program, designed to facilitate the development and expedite the review of drugs to treat serious diseases, fill unmet medical needs, and get important new drugs to patients earlier. Ravicti also was granted orphan product designation because it is intended to treat a rare disease.
Glycerol phenylbutyrate (HPN-100) is a pro-drug of phenylbutryrate and a pre-pro-drug of phenylacetic acid (PAA), the active moiety of Buphenyl, the only therapy currently FDA-approved as adjunctive therapy for the chronic management of patients with the most prevalent urea cycle disorders — carbamylphosphate synthetase, ornithine transcarbamylase, and argininosuccinic acid synthetase. HPN-100, which is dosed orally in liquid form, provides an alternative pathway to the urea cycle for the disposal of waste nitrogen through the renal excretion of phenylacetylglutamine, which is formed from PAA and glutamine.
RAVICTI (glycerol phenylbutyrate) is a clear, colorless to pale yellow oral liquid. It is insoluble in water and most organic solvents, and it is soluble in dimethylsulfoxide (DMSO) and > 65% acetonitrile.
Glycerol phenylbutyrate is a nitrogen-binding agent. It is a triglyceride containing 3 molecules of PBA linked to a glycerol backbone, the chemical name of which is benzenebutanoic acid, 1′, 1′ ‘ –(1,2,3-propanetriyl) ester with a molecular weight of 530.67. It has a molecular formula of C33H38O6.
DR ANTHONY MELVIN CRASTO
ORGANIC SPECTROSCOPY
New Drug Approvals 