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Investigational Antiviral Drugs
Published in M. Lindsay Grayson, Sara E. Cosgrove, Suzanne M. Crowe, M. Lindsay Grayson, William Hope, James S. McCarthy, John Mills, Johan W. Mouton, David L. Paterson, Kucers’ The Use of Antibiotics, 2017
John Mills, Suzanne M. Crowe, Marianne Martinello
Voxilaprevir (GS-9857) is a pangenotypic second-generation NS3/4A protease inhibitor undergoing phase III clinical trials as part of an oral once daily fixed-dose combination DAA regimen co-formulated with sofosbuvir (a nucleotide polymerase inhibitor) and velpatasvir (NS5A assembly inhibitor) as the combination of sofosbuvir–velpatasvir–voxilaprevir 400/100/100 mg. Phase II efficacy and safety results were encouraging with short-duration therapy (NCT02202980). Among treatment-naive cirrhotic and noncirrhotic participants with HCV GT1 and GT-3, SVR12 ranged between 83% and 93% after only 6 weeks of sofosbuvir–velpatasvir–voxilaprevir. In treatment-experienced (DAA drug naive) cirrhotic and noncirrhotic participants with HCV GT-1 and GT-3 receiving 8 weeks of sofosbuvir–velpatasvir–voxilaprevir, SVR12 was 100%, falling to 89% in participants with HCV GT-1 who had failed protease inhibitor–based triple therapy. Small numbers of participants who had failed an oral interferon-free regimen were included; 6 weeks of sofosbuvir–velpatasvir–voxilaprevir was suboptimal in GT-1 (SVR12: 67%; 20/30), but 8 weeks was more promising in GT-3 (SVR12: 100%; 4/4). The most commonly reported adverse events were headache, nausea, and fatigue. Phase III trial results comparing sofosbuvir–velpatasvir–voxilaprevir (8 or 12 weeks) with sofosbuvir–velpatasvir (12 weeks) were expected in 2016, including experienced participants previously treated with earlier direct-acting antiviral drugs (Gane et al., 2016a; Gane et al., 2016b).
Direct antiviral agents (DAAs) and their use in pregnant women with hepatitis C (HCV)
Published in Expert Review of Anti-infective Therapy, 2022
Sandra Abdul Massih, Ahizechukwu C. Eke
is available as a fixed dose combination of 400 mg SOF with 100 mg VEL, dosed once daily [37]. Velpatasvir is highly bound to plasma proteins (approximately 99.5% bound), and is metabolized by CYP2B6, CYP2C8, and CYP3A4, and primarily excreted through the biliary route. Velpatasvir has a half-life of approximately 15 hours [37]. SOF/VEL combination is also available in combination with a third drug, Voxilaprevir (VPR) as Sofosbuvir/Velpatasvir/Voxilaprevir (SOF/VEL/VOX) [38]. The SOF/VEL/VOX regimen is highly effective against all HCV genotypes, dosed as one-tablet daily of SOF 400 mg/ VEL 100 mg/ and VPR 100 mg [38]. Voxilaprevir has a Tmax of approximately 4 hours, and is generally well absorbed following oral administration, and shows increased absorption with food (increase between 112% and 435%) [38]. Voxilaprevir is mainly metabolized by CYP3A4, and eliminated in feces with a half-life of 33 hours [38].
An evaluation of ledipasvir + sofosbuvir for the treatment of chronic hepatitis C infection
Published in Expert Opinion on Pharmacotherapy, 2021
Pearson Balatow, Amber Sandlin, Theodore James Cory
There are multiple HCV drugs currently on the market. Interferon therapy was the standard of care for years, but the development of new combination therapies has significantly decreased the role of interferon in HCV treatment. LDV/SOF was approved in 2014 followed by a rapid rise in combination HCV therapy approvals over a few years. The current market for combination HCV therapy is saturated with options. Elbasvir/grazoprevir was approved in 2016 for genotypes 1 and 4. Sofosbuvir/velpatasvir/voxilaprevir was approved in 2017 to treat any HCV genotype. This drug combination is also indicated for individuals who have had failure of treatment with sofosbuvir treatment alone. Glecaprevir/pibrentasvir was also approved in 2017 for the treatment of all HCV genotypes. It possesses the advantage of an 8-week treatment regimen.
Developments in the treatment of HCV genotype 3 infection
Published in Expert Review of Anti-infective Therapy, 2019
Retreatment options are limited for GT3 patients failing NS5A drug-based regimens. GLE/PIB is not recommended for the retreatment of patients with prior exposure to NS3 protease and/or NS5A-inhibitors [66]. For patients failing other approved NS5A drug-based regimens, SOF/VEL plus the next-generation NS3 protease inhibitor, voxilaprevir (VOX) is a recently approved retreatment option [84,85]. In the POLARIS-1 retreatment study, 5% (4/83) of patients relapsed after 12 weeks of SOF/VEL/VOX treatment. All four failures had cirrhosis and three had baseline NS5A RASs A30K or Y93H also detected at relapse, and one had emergent E92K [85]. The NS5A-E92K substitution confers no resistance to VEL [59]. In a follow-up resistance analysis of GT3a patients treated with SOF/VEL/VOX [86], 93% with baseline Y93H achieved SVR (Table 1). It was noted that a few patients with highly resistant A30K-L31M (N = 2), A30K-Y93H (N = 1), L31F-Y93H (N = 1) and M28G (N=1) achieved SVR, however, the cirrhosis status of these patients was not described.