Sofosbuvir

Sofosbuvir

File:PSI-7977.svg
Clinical data
Trade names	Sovaldi, Virunon
Synonyms	PSI-7977; GS-7977
[[Regulation of therapeutic goods |Template:Engvar data]]	US FDA: Sofosbuvir
Pregnancy category	US: B (No risk in non-human studies)
ATC code	J05AB (WHO)
Legal status
Legal status	US: ℞-only
Identifiers
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
CAS Number	1190307-88-0
ChemSpider	26286922
UNII	WJ6CA3ZU8B
E number	{{#property:P628}}
ECHA InfoCard	{{#property:P2566}}
Chemical and physical data
Formula	C22H29FN3O9P
Molar mass	529.46 g·mol−1
3D model (JSmol)	Interactive image
SMILES C[C@@H](C(=O)OC(C)C)N[P@](=O)(OC[C@@H]1[C@H]([C@@]([C@@H](O1)n2ccc(=O)[nH]c2=O)(C)F)O)Oc3ccccc3
InChI InChI=1S/C22H29FN3O9P/c1-13(2)33-19(29)14(3)25-36(31,35-15-8-6-5-7-9-15)32-12-16-18(28)22(4,23)20(34-16)26-11-10-17(27)24-21(26)30/h5-11,13-14,16,18,20,28H,12H2,1-4H3,(H,25,31)(H,24,27,30)/t14-,16+,18+,20+,22+,36-/m0/s1 Key:TTZHDVOVKQGIBA-IQWMDFIBSA-N

Sofosbuvir (brand names Sovaldi and Virunon) is a drug used for hepatitis C virus (HCV) infection, with a high cure rate. 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.

Sofosbuvir is the first all-oral, Interferon-free regimen approved for treating chronic Hepatitis C.

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. Sofosbuvir treatment regimens last 12 weeks for genotypes 1, 2 and 4, compared to 24 weeks for treatment of genotype 3. 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.

Mechanism of Action

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

FDA Approval

The New Drug Application for Sofosbuvir was submitted on April 8, 2013 and received the FDA's Breakthrough Therapy Designation, which grants priority review status to drug candidates that may offer major treatment advantages over existing options.

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

Medical uses

Sofosbuvir is being studied in combination with pegylated interferon and ribavirin, with ribavirin alone, and with other direct-acting antiviral agents. It has shown 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.

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.

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. Gilead has developed a sofosbuvir + ledipasvir coformulation that is being tested with and without ribavirin.

Cost

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. This represents a substantial pricing increase from previous treatments consisting of Interferon and Ribavirin, which were valued between 15,000-20,000 dollars. The price is also significantly higher than that of Johnson & Johnson's recently approved drug Olysio, which is valued at $50,000 and also treats chronic Hepatitis C. The high cost of the drug has resulted in a push back from insurance companies and the like, including Express Scripts, which has threatened to substitute lower priced competitors, even if those therapies come with a more unfriendly dosing schedule. Other treatments that have recently entered the market have not matched the efficacy of Sofosbuvir, however, allowing Gilead to name its price until additional competition enters the market. Patient advocates such as Doctors Without Borders have complained about the price, which is particularly difficult for underdeveloped countries to afford.

Information about related patents

Patents: US patent number 7964580, US patent number 8415322, US patent number 8334270,US patent number 7429572 Patent Expiration Date: March 26, 2029 for US patent number 7964580 and 8334270 (2028 in EU)； April 3, 2025 for US patent number 7429572 and 8415322