Sofosbuvir/velpatasvir/voxilaprevir

Sofosbuvir/velpatasvir/voxilaprevir, sold under the brand name Vosevi, is a fixed-dose combination medication for the treatment of hepatitis C. It contains sofosbuvir, a hepatitis C virus (HCV) nucleotide analog NS5B polymerase inhibitor; velpatasvir, an HCV NS5A inhibitor; and voxilaprevir an HCV NS3/4A protease inhibitor.^[2][5]

Sofosbuvir/velpatasvir/voxilaprevir

Combination of
Sofosbuvir	NS5B RNA polymerase inhibitor
Velpatasvir	NS5A inhibitor
Voxilaprevir	NS3/4A protease inhibitor
Clinical data
Trade names	Vosevi
AHFS/Drugs.com	Monograph
MedlinePlus	a617037
License data	US DailyMed: Vosevi
Pregnancy category	AU: B1
Routes of administration	By mouth (tablets)
ATC code	J05AP56 (WHO)
Legal status
Legal status	AU: S4 (Prescription only) CA: ℞-only[1] US: ℞-only[2] EU: Rx-only[3][4]
Identifiers
PubChem CID	129011857
KEGG	D10900
Chemical and physical data
Formula	C111H135F5N17O26PS
Molar mass	2281.42 g·mol−1
3D model (JSmol)	Interactive image
SMILES CCC1C2CN(C1C(=O)NC3(CC3C(F)F)C(=O)NS(=O)(=O)C4(CC4)C)C(=O)C(NC(=O)OC5CC5CCCCC(C6=NC7=C(C=C(C=C7)OC)N=C6O2)(F)F)C(C)(C)C.CC1CCC(N1C(=O)C(C(C)C)NC(=O)OC)C2=NC3=C(N2)C=CC4=CC5=C(C=C43)OCC6=C5C=CC(=C6)C7=CN=C(N7)C8CC(CN8C(=O)C(C9=CC=CC=C9)NC(=O)OC)COC.CC(C)OC(=O)C(C)NP(=O)(OCC1C(C(C(O1)N2C=CC(=O)NC2=O)(C)F)O)OC3=CC=CC=C3
InChI InChI=1S/C49H54N8O8.C40H52F4N6O9S.C22H29FN3O9P/c1-26(2)41(54-48(60)63-5)47(59)57-27(3)12-17-38(57)45-51-36-16-14-30-20-35-33-15-13-31(19-32(33)25-65-40(35)21-34(30)43(36)53-45)37-22-50-44(52-37)39-18-28(24-62-4)23-56(39)46(58)42(55-49(61)64-6)29-10-8-7-9-11-29;1-7-22-27-19-50(28(22)32(51)48-39(18-23(39)31(41)42)35(53)49-60(55,56)38(5)14-15-38)34(52)30(37(2,3)4)47-36(54)59-26-16-20(26)10-8-9-13-40(43,44)29-33(58-27)46-25-17-21(57-6)11-12-24(25)45-29;1-13(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/h7-11,13-16,19-22,26-28,38-39,41-42H,12,17-18,23-25H2,1-6H3,(H,50,52)(H,51,53)(H,54,60)(H,55,61);11-12,17,20,22-23,26-28,30-31H,7-10,13-16,18-19H2,1-6H3,(H,47,54)(H,48,51)(H,49,53);5-11,13-14,16,18,20,28H,12H2,1-4H3,(H,25,31)(H,24,27,30)/t27-,28-,38-,39-,41-,42+;20-,22-,23+,26-,27+,28+,30-,39-;14-,16+,18+,20+,22+,36-/m010/s1 Key:FMWRYUBVSONSCK-ZYTFCPLVSA-N

The most common adverse reactions include headache, fatigue, diarrhea, and nausea.^[6]

The combination was approved for medical use in the United States and in the European Union in July 2017.^[6][3] Vosevi is sold by Gilead Sciences.^[6]

Medical uses

In the US, sofosbuvir/velpatasvir/voxilaprevir is indicated for the treatment of adults with chronic hepatitis C virus infection without cirrhosis (liver disease) or with compensated cirrhosis (Child-Pugh A).^[2][6]

In the EU, it is indicated for the treatment of chronic hepatitis C virus infection in people aged twelve years of aged and older and weighing at least 30 kilograms (66 lb).^[3][4]

Adverse effects

The FDA label for sofosbuvir/velpatasvir/voxilaprevir contains a boxed warning about the risk of Hepatitis B virus reactivation.^[2]

History

The safety and efficacy of sofosbuvir/velpatasvir/voxilaprevir was evaluated in two phase III clinical trials that enrolled approximately 750 adults without cirrhosis or with mild cirrhosis.^[6] The first trial compared twelve weeks of treatment with the combination versus treatment with placebo in adults with genotype 1 who had previously failed treatment with an NS5A inhibitor drug.^[6] Participants with genotypes 2, 3, 4, 5, or 6 all received the combination.^[6] The second trial compared twelve weeks of treatment with the combination versus treatment with the previously approved drugs sofosbuvir and velpatasvir in adults with genotypes 1, 2, or 3 who had previously failed treatment with sofosbuvir but not an NS5A inhibitor drug.^[6] Results of both trials demonstrated that 96-97 percent of participants who received the combination had no virus detected in the blood 12 weeks after finishing treatment, suggesting that participants’ infection had been cured.^[6]

The US Food and Drug Administration (FDA) granted the application for sofosbuvir/velpatasvir/voxilaprevir priority review and breakthrough therapy designations.^[6] The FDA granted approval of Vosevi to Gilead Sciences Inc.^[6]