Sofosbuvir

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Systematic (IUPAC) name
Isopropyl (2S)-2-[[[(2R,3R,4R,5R)-5-(2,4-dioxopyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydrofuran-2-yl]methoxy-phenoxy-phosphoryl]amino]propanoate
Clinical data
Trade namesSovaldi, Virunon
Pregnancy cat. ?
Legal status ?
Identifiers
CAS number1190307-88-0
ATC codeJ05AB
ChemSpider26286922
UNIIWJ6CA3ZU8B YesY
SynonymsPSI-7977; GS-7977
Chemical data
FormulaC22H29FN3O9P 
 
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Systematic (IUPAC) name
Isopropyl (2S)-2-[[[(2R,3R,4R,5R)-5-(2,4-dioxopyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydrofuran-2-yl]methoxy-phenoxy-phosphoryl]amino]propanoate
Clinical data
Trade namesSovaldi, Virunon
Pregnancy cat. ?
Legal status ?
Identifiers
CAS number1190307-88-0
ATC codeJ05AB
ChemSpider26286922
UNIIWJ6CA3ZU8B YesY
SynonymsPSI-7977; GS-7977
Chemical data
FormulaC22H29FN3O9P 

Sofosbuvir (brand names Sovaldi and Virunon) is a drug used for hepatitis C.[1][2] It inhibits the RNA polymerase that the hepatitis C virus uses to replicate its RNA. It was discovered at Pharmasset and then acquired for development by Gilead Sciences.[3]

On 6th December 2013, the U.S. Food and Drug Administration approved Sovaldi for the treatment of chronic hepatitis C.[4]

Sofosbuvir will cost $84,000 for 12 weeks of treatment used for genotype 1 and 2, and $168,000 for the 24 weeks used for genotype 3.[5]

Mechanism of Action[edit]

Sofosbuvir is a prodrug that is metabolized to the active antiviral agent 2'-deoxy-2'-α-fluoro-β-C-methyluridine-5'-monophosphate.[6] Sofosbuvir is a nucleotide analogue inhibitor of the hepatitis C virus (HCV) polymerase.[7] The HCV polymerase or NS5B protein is a RNA-dependent RNA polymerase critical for the viral cycle.

Clinical studies[edit]

Sofosbuvir is being studied in combination with pegylated interferon and ribavirin, with ribavirin alone, and with other direct-acting antiviral agents.[8][9] It has shown excellent clinical efficacy when used either with pegylated interferon/ribavirin or in interferon-free combinations. In particular, combinations of sofosbuvir with NS5A inhibitors, such as daclatasvir or GS-5885, have shown sustained virological response rates of up to 100% in people infected with HCV.[10]

Data from the ELECTRON trial showed that a dual interferon-free regimen of sofosbuvir plus ribavirin produced a 24-week post-treatment sustained virological response (SVR24) rate of 100% for previously untreated patients with HCV genotypes 2 or 3.[11][12]

Data presented at the 20th Conference on Retroviruses and Opportunistic Infections in March 2013 showed that a triple regimen of sofosbuvir, ledipasvir, and ribavirin produced a 12-week post-treatment sustained virological response (SVR12) rate of 100% for both treatment-naive patients and prior non-responders with HCV genotype 1.[13] Gilead has developed a sofosbuvir + ledipasvir coformulation that is being tested with and without ribavirin.

References[edit]

  1. ^ News: United States to approve potent oral drugs for hepatitis C, Sara Reardon, Nature, 30 October 2013
  2. ^ 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 (October 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. 
  3. ^ "PSI-7977". Gilead Sciences. 
  4. ^ "FDA approves Sovaldi for chronic hepatitis C". FDA New Release. U.S. Food and Drug Administration. 2013-12-06. 
  5. ^ Pollack A (December 6, 2013). "F.D.A. Approves Pill to Treat Hepatitis C". NYTimes.com. 
  6. ^ Murakami E, Tolstykh T, Bao H, Niu C, Steuer HM, Bao D, Chang W, Espiritu C, Bansal S, Lam AM, Otto MJ, Sofia MJ, Furman PA (November 2010). "Mechanism of activation of PSI-7851 and its diastereoisomer PSI-7977". J. Biol. Chem. 285 (45): 34337–47. doi:10.1074/jbc.M110.161802. PMC 2966047. PMID 20801890. 
  7. ^ Alejandro Soza (November 11, 2012). "Sofosbuvir". Hepaton. 
  8. ^ Murphy T (November 21, 2011). "Gilead Sciences to buy Pharmasset for $11 billion". Bloomberg Businessweek. 
  9. ^ Asselah T (January 2014). "Sofosbuvir for the treatment of hepatitis C virus". Expert Opin Pharmacother 15 (1): 121–30. doi:10.1517/14656566.2014.857656. PMID 24289735. 
  10. ^ "AASLD 2012: Sofosbuvir and daclatasvir dual regimen cures most people with HCV genotypes 1, 2, or 3". News. European Liver Patients Association. 2012-11-21. 
  11. ^ AASLD: PSI-7977 plus Ribavirin Can Cure Hepatitis C in 12 Weeks without Interferon. Highleyman, L. HIVandHepatitis.com. 8 November 2011.
  12. ^ Gane EJ, Stedman CA, Hyland RH, Ding X, Svarovskaia E, Symonds WT, Hindes RG, Berrey MM (January 2013). "Nucleotide polymerase inhibitor sofosbuvir plus ribavirin for hepatitis C". N. Engl. J. Med. 368 (1): 34–44. doi:10.1056/NEJMoa1208953. PMID 23281974. 
  13. ^ CROI 2013: Sofosbuvir + Ledipasvir + Ribavirin Combo for HCV Produces 100% Sustained Response. Highleyman, L. HIVandHepatitis.com. 4 March 2013.