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Gastroenterology. 2017 Jul;153(1):113-122. doi: 10.1053/j.gastro.2017.03.047. Epub 2017 Apr 5.

Efficacy of 8 Weeks of Sofosbuvir, Velpatasvir, and Voxilaprevir in Patients With Chronic HCV Infection: 2 Phase 3 Randomized Trials.

Author information

1
Mount Sinai Beth Israel, New York, New York; Icahn School of Medicine at Mount Sinai, New York, New York. Electronic address: ira.jacobson@nyumc.org.
2
Texas Liver Institute, University of Texas Health Science Center, San Antonio, Texas.
3
New Zealand Liver Transplant Unit, Auckland City Hospital, Auckland, New Zealand.
4
Centre Hospitalier de l'Université de Montréal, Montréal, Québec, Canada.
5
Ruane Medical and Liver Health Institute, Los Angeles, California.
6
ID Care, Hillsborough, New Jersey.
7
William Osler Health System, Brampton Civic Hospital, Brampton, Ontario, Canada.
8
University of Alberta, Edmonton, Alberta, Canada.
9
Emory University, Atlanta, Georgia.
10
Atlanta Medical Center, Atlanta, Georgia.
11
Gilead Sciences, Inc, Foster City, California.
12
James J. Peters Veterans Affairs Medical Center, Bronx, New York; Icahn School of Medicine at Mount Sinai, New York, New York.
13
Medical Department of Hepatology and Gastroenterology, Charité Universitätsmedizin Berlin, Berlin, Germany.
14
Institute of Liver Studies, Kings College Hospital, London, United Kingdom.
15
Gastroenterology and Nutritional Medical Services, Bastrop, Louisiana.
16
Digestive Care, South Florida Center of Gastroenterology, Wellington, Florida.
17
Toronto Western Hospital Liver Centre, Toronto, Ontario, Canada.
18
St Vincent's Hospital Sydney, University of New South Wales Sydney, Sydney, New South Wales, Australia; Kirby Institute, University of New South Wales Sydney, Sydney, New South Wales, Australia.
19
Christchurch Hospital, University of Otago, Christchurch, New Zealand.
20
St. Vincent's Hospital, Melbourne, Victoria, Australia.
21
Hôpital Beaujon, Université Paris Diderot, INSERM UMR 1149, Centre de Recherche sur l'Inflammation, Clichy, France.
22
Alfred Hospital, Melbourne, Victoria, Australia.
23
Royal London Hospital, London, United Kingdom.

Abstract

BACKGROUND & AIMS:

Patients with chronic hepatitis C virus (HCV) infection have high rates of sustained virologic response (SVR) after 12 weeks of treatment with the nucleotide polymerase inhibitor sofosbuvir combined with the NS5A inhibitor velpatasvir. We assessed the efficacy of 8 weeks of treatment with sofosbuvir and velpatasvir plus the pangenotypic NS3/4A protease inhibitor voxilaprevir (sofosbuvir-velpatasvir-voxilaprevir).

METHODS:

In 2 phase 3, open-label trials, patients with HCV infection who had not been treated previously with a direct-acting antiviral agent were assigned randomly to groups given sofosbuvir-velpatasvir-voxilaprevir for 8 weeks or sofosbuvir-velpatasvir for 12 weeks. POLARIS-2, which enrolled patients infected with all HCV genotypes with or without cirrhosis, except patients with genotype 3 and cirrhosis, was designed to test the noninferiority of 8 weeks of sofosbuvir-velpatasvir-voxilaprevir to 12 weeks of sofosbuvir-velpatasvir using a noninferiority margin of 5%. POLARIS-3, which enrolled patients infected with HCV genotype 3 who had cirrhosis, compared rates of SVR in both groups with a performance goal of 83%.

RESULTS:

In POLARIS-2, 95% (95% confidence interval [CI], 93%-97%) of patients had an SVR to 8 weeks of sofosbuvir-velpatasvir-voxilaprevir; this did not meet the criterion to establish noninferiority to 12 weeks of sofosbuvir-velpatasvir, which produced an SVR in 98% of patients (95% CI, 96%-99%; difference in the stratum-adjusted Mantel-Haenszel proportions of -3.2%; 95% CI, -6.0% to -0.4%). The difference in the efficacy was owing primarily to a lower rate of SVR (92%) among patients with HCV genotype 1a infection receiving 8 weeks of sofosbuvir-velpatasvir-voxilaprevir. In POLARIS-3, 96% of patients (95% CI, 91%-99%) achieved an SVR in both treatment groups, which was significantly superior to the performance goal. Overall, the most common adverse events were headache, fatigue, diarrhea, and nausea; diarrhea and nausea were reported more frequently by patients receiving voxilaprevir. In both trials, the proportion of patients who discontinued treatment because of adverse events was low (range, 0%-1%).

CONCLUSIONS:

In phase 3 trials of patients with HCV infection, we did not establish that sofosbuvir-velpatasvir-voxilaprevir for 8 weeks was noninferior to sofosbuvir-velpatasvir for 12 weeks, but the 2 regimens had similar rates of SVR in patients with HCV genotype 3 and cirrhosis. Mild gastrointestinal adverse events were associated with treatment regimens that included voxilaprevir. ClinicalTrials.gov numbers: POLARIS-2, NCT02607800; and POLARIS-3, NCT02639338.

KEYWORDS:

Clinical Trial; Comparison; Direct-Acting Antiviral Agent; Shortened Duration Therapy

PMID:
28390869
DOI:
10.1053/j.gastro.2017.03.047
[Indexed for MEDLINE]

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