By William Elliott, MD, FACP, and James Chan, PharmD, PhD
Dr. Elliott is Medical Director, Pharmacy, Northern California Kaiser Permanente, and Assistant Clinical Professor
of Medicine, University of California, San Francisco. Dr. Chan is Pharmacy Quality and Outcomes Manager, Kaiser Permanente, Oakland, CA.
Drs. Elliott and Chan report no financial relationships relevant to this field of study.
The FDA has approved the first drug combination for the treatment of all six major genotypes of hepatitis C virus (HCV) infections. The combination contains a previously approved nucleotide analog NS5B polymerase inhibitor, sofosbuvir (SOF), and a newly approved HCV NS5A inhibitor velpatasvir (VEL). SOF/VEL is marketed as Epclusa.
SOF/VEL is indicated for the treatment of adult patients with chronic HCV genotype 1, 2, 3, 4, 5, or 6 infections.1 It is approved for patients without cirrhosis, with compensated cirrhosis, or with decompensated cirrhosis (in combination with ribavirin).
For patients without cirrhosis or with compensated cirrhosis, the recommended dose is one tablet once daily for 12 weeks.1 For patients with decompensated cirrhosis, the recommended dose is one tablet with weight-based ribavirin for 12 weeks. No dose adjustments are needed for mild-to-moderate renal impairment or mild, moderate, or severe hepatic impairment. Each tablet of SOF/VEL contains 400 mg of sofosbuvir and 100 mg of velpatasvir.
This is the first drug/drug combination approved for the treatment of the six most prevalent HCV genotypes, as well as for patients with or without cirrhosis.
Coadministration of sofosbuvir and amiodarone is not recommended because of potential risk of serious symptomatic bradycardia.1 Concomitant use with P-gp inducers or moderate to potent inducers of CYP2B6, CYP2C8, or CYP3A4 also is not recommended. Take precautions with concomitant administration with antacids or histamine-2 receptor antagonists. Avoid proton pump inhibitors unless medically necessary.1
The safety and efficacy of SOF/VEL were evaluated in three trials in patients without cirrhosis or with compensated cirrhosis.1,2,3 A fourth included subjects presenting with decompensated cirrhosis.1,4 The primary endpoint was no detectable virus at 12 weeks post-treatment (SVR12).
In the first study, subjects with genotype 1, 2, 4, 5, and 6 were randomized to SOF/VEL for 12 weeks (n = 624) or placebo (n = 116).1,2 SVR12 ranged from 97% to 100%, compared to 0% for placebo.
Study two compared SOF/VEL for 12 weeks (n = 134) to SOF + ribavirin for 12 weeks (n = 132) in subjects with genotype 2.1,3 SVR12 rates were 99% vs. 94%. Relapse rates were 0% vs. 5%, respectively.
Study three compared SOF/VEL for 12 weeks (n = 277) and SOF + ribavirin for 24 weeks (n = 275) in subjects with genotype 3.1,3 Overall, SVR12 rates were 95% compared to 80% (treatment difference of 14.8%; 95% confidence interval, 9.6-20%). SOF/VEL was more effective in treatment-naïve and treatment-experienced without cirrhosis (98% vs. 90%; 94% vs. 71%, respectively). In those with compensated cirrhosis, SVR12 rates were 93% vs. 73%, and 89% vs. 58%, respectively.
Study four compared three regimens: SOF/VEL for 12 weeks, SOF/VEL + ribavirin for 12 weeks, or SOF/VEL for 24 weeks in subjects with genotype 1, 2, 3, 4, and 6 with decompensated cirrhosis.1,4 Overall, SVR12 rates were 83%, 94%, and 86%, respectively. The most frequently reported adverse events for monotherapy included headache (22%) and fatigue (15%).1 In combination with ribavirin, adverse events included fatigue (32%), anemia (26%), nausea (15%), headache (11%), insomnia (11%), and diarrhea (10%).
SOF/VEL has been highly anticipated, as it is the first combination that provides an effective treatment for all genotypes as well as patients presenting with moderate-to-severe cirrhosis. The cost of SOF/VEL (without ribavirin) is $74,760 for 12 weeks of therapy.
- Epclusa Prescribing Information. Gilead Sciences. June 2016.
- Feld JJ, Jacobson IM, Hézode C, et al. Sofosbuvir and velpatasvir for HCV genotype 1, 2, 4, 5, and 6 infection. N Engl J Med 2015;373:2599-2607.
- Foster GR, Afdhal N, Roberts SK, et al. Sofosbuvir and velpatasvir for HCV genotype 2 and 3 infection. N Engl J Med 2015;373:2608-2617.
- Curry MP, O’Leary JG, Bzowej N, et al. Sofosbuvir and velpatasvir for HCV in patients with decompensated cirrhosis. N Engl J Med 2015;373:2618-2628.