SandboxAlonso
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sheng Shi, M.D. [2]
Synonyms and keywords: Sovaldi and Virunon
Overview
Simeprevir (formerly TMC435; trade name Olysio) is a drug for the treatment and cure of hepatitis C.[1] It was developed by Sofosbuvir (brand names Sovaldi and Virunon) is a drug used for hepatitis C virus (HCV) infection, with a high cure rate.[2][3] It inhibits the RNA polymerase that the hepatitis C virus uses to replicate its RNA. It was discovered at Pharmasset and developed by Gilead Sciences.[4]
Sofosbuvir is the first all-oral, Interferon-free regimen approved for treating chronic Hepatitis C.[5]
In 2013, the FDA approved sofosbuvir in combination with ribavirin (RBV) for oral dual therapy of HCV genotypes 2 and 3, and for triple therapy with injected pegylated interferon (pegIFN) and RBV for treatment-naive patients with HCV genotypes 1 and 4.[5] Sofosbuvir treatment regimens last 12 weeks for genotypes 1, 2 and 4, compared to 24 weeks for treatment of genotype 3.[6] Sofosbuvir will cost $84,000 for 12 weeks of treatment and $168,000 for the 24 weeks, which some patient advocates have criticized as unaffordable.
Interferon-free therapy for treatment of Hepatitis C eliminates the substantial side-effects associated with use of Interferon. Up to half of Hepatitis C patients cannot tolerate the use of Interferon.[7]
Category
Antiviral
US Brand Names
SOVALDI®
FDA Package Insert
Description | Clinical Pharmacology | Microbiology | Indications and Usage | Contraindications | Warnings and Precautions | Adverse Reactions | Drug Interactions | Overdosage | Clinical Studies | Dosage and Administration | How Supplied | Labels and Packages
Mechanism of Action
Sofosbuvir is an inhibitor of the HCV NS5B RNA-dependent RNA polymerase, which is essential for viral replication. Sofosbuvir is a nucleotide prodrug that undergoes intracellular metabolism to form the pharmacologically active uridine analog triphosphate (GS-461203), which can be incorporated into HCV RNA by the NS5B polymerase and acts as a chain terminator. In a biochemical assay, GS-461203 inhibited the polymerase activity of the recombinant NS5B from HCV genotype 1b, 2a, 3a and 4a with IC50 values ranging from 0.7 to 2.6 µM. GS-461203 is not an inhibitor of human DNA and RNA polymerases nor an inhibitor of mitochondrial RNA polymerase.
- ↑ News: United States to approve potent oral drugs for hepatitis C, Sara Reardon, Nature, 30 October 2013
- ↑ News: United States to approve potent oral drugs for hepatitis C, Sara Reardon, Nature, 30 October 2013
- ↑ Sofia MJ, Bao D, Chang W, Du J, Nagarathnam D, Rachakonda S, Reddy PG, Ross BS, Wang P, Zhang HR, Bansal S, Espiritu C, Keilman M, Lam AM, Steuer HM, Niu C, Otto MJ, Furman PA (2010). "Discovery of a β-d-2'-deoxy-2'-α-fluoro-2'-β-C-methyluridine nucleotide prodrug (PSI-7977) for the treatment of hepatitis C virus". J. Med. Chem. 53 (19): 7202–18. doi:10.1021/jm100863x. PMID 20845908. Unknown parameter
|month=ignored (help) - ↑ "PSI-7977". Gilead Sciences.
- ↑ 5.0 5.1 Tucker M (December 6, 2013). "FDA Approves 'Game Changer' Hepatitis C Drug Sofosbuvir". Medscape.
- ↑ "U.S. Food and Drug Administration Approves Gilead's Sovaldi™ (Sofosbuvir) for the Treatment of Chronic Hepatitis C - See more at:http://www.gilead.com/news/press-releases/2013/12/us-food-and-drug-administration-approves-gileads-sovaldi-sofosbuvir-for-the-treatment-of-chronic-hepatitis-c#sthash.T9uTbSWK.dpuf". Gilead. December 6, 2013. External link in
|title=(help) - ↑ "Sofosbuvir is safer than interferon for hepatitis C patients, say scientists". News Medical. April 25, 2013.