Sofosbuvir Tablets (Sovaldi)
By William T. Elliott, MD, FACP, and James Chan, PharmD, PhD
Dr. Elliott is Chair, Formulary Committee, Northern California Kaiser Permanente; and Assistant 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 first nucleotide analog polymerase inhibitor has been approved for the treatment of hepatitis C virus (HCV) infection. Sofosbuvir is marketed by Gilead as Sovaldi.
Sofosbuvir is indicated for the treatment of patients with hepatitis C infections (genotype 1, 2, 3, or 4).1 This includes patients with hepatocellular carcinoma meeting Milan criteria (awaiting liver transplantation) and those who are coinfected with HCB and HIV-1 viruses.
Sofosbuvir is taken once daily without regard to meals. For genotype 1 or 4, it is taken with peginterferon-alpha and ribavirin (PR) for 12 weeks. For genotype 2, sofosbuvir is taken with ribavirin only for 12 weeks and for genotype 3, 24 weeks.
Sofosbuvir is available as 400 mg tablets.
Sofosbuvir offers a low pill burden and the shortest duration of treatment to date (12 weeks total for genotype 1, 2, and 4). Sofosbuvir provides an interferon-free regimen for HCV genotype 2 and 3 and for patients with genotype 1 infection in whom interferon is not appropriate.
Anemia was reported in 21% of patients compared to 12% for PR.1 Coadministration of enzyme-induced antiepileptic drugs should be avoided.
Sofosbuvir is a new class of anti-HCV drug. It is a nucleotide analog HCV NS5B RNA polymerase inhibitor. It differs from the previously approved non-structure protein protease inhibitors (boceprevir, telaprevir, and simeprevir). The efficacy and safety were evaluated in five phase 3 studies, one in treatment-naïve subjects with HCV genotype 1 or 4, three in various treatment-naïve and interferon-experienced HCV genotype 2 or 3 subjects, and one in subjects coinfected with HCV genotype 1, 2, or 3 and HIV.1,2,3 One treatment-naïve study used an open-label design. Subjects infected with genotype 1 or 4 (n = 327) were administered sofosbuvir (400 mg once daily) with PR for 12 weeks.1,2 The second was a noninferiority study. Those infected with HCV genotype 2 or 3 were randomized to sofosbuvir + ribavirin for 12 weeks (n = 256) or PR for 24 weeks (n = 243). The primary efficacy endpoint was sustained virologic response at 12 weeks after end of therapy (SVR12). SVR12 was 89% for genotype 1a, 82% for genotype 1b, and 96% for genotype 4. Overall, sofosbuvir was less effective in those with cirrhosis than in those without (80% vs 92%), and lowest in those with multiple factors, genotype 1, Metavir score F3/F4 fibrosis, non-CC IL28B, and baseline RNA > 800,000 IU/mL (71%). For treatment-naïve genotype 2 and 3 infected subjects, sofosbuvir + ribavirin was noninferior to PR overall. For genotype 2, sofosbuvir + ribavirin was more effective than PR (95% vs 78%) and numerically less effective for genotype 3 (56% vs 63%). Similarly, those with cirrhosis did not do as well. Two studies evaluated different durations of treatment (12, 16, and 24 weeks) with sofosbuvir and ribavirin in treatment-naïve and previously treated subjects. For genotype 2 infections, treatment longer than 12 weeks did not result in significant improvement in SVR12. For genotype 3 infections, the optimal dosing for sofosbuvir + ribavirin was determined to be 24 weeks. With 24 weeks of treatment of genotype 3 infections, SVR12 was 93% for treatment-naïve and 77% for treatment-experienced subjects. One open-label trial was conducted in subjects coinfected with HCV 1, 2, or 3 with HIV-1.1 Genotype 2 subjects were given sofosbuvir + ribavirin for 12 weeks and genotype 1 and 3 subjects were given sofosbuvir + ribavirin for 24 weeks. Overall, SVR12 rates were 88%, 78%, and 92% for genotype 2, 1, and 3, respectively. Sofosbuvir is well tolerated; the treatment discontinuation rates were 2% for sofosbuvir + PR for 12 weeks, 1% for sofosbuvir + ribavirin for 12 weeks, and 11% for PR for 24 weeks.1,2
Sofosbuvir is the first nucleotide analog polymerase inhibitor to be approved for the treatment of HCV, and provides a treatment option for many HCV patients who have not been candidates for treatment previously. It is an option for all HCV genotypes and provides an advancement in the treatment of HCV infections. The wholesale cost for 4 weeks of SOF therapy is $28,000.
- Sovaldi Prescribing Information. Foster City, CA: Gilead Sciences, Inc. December 2013.
- Lawitz E, et al. Sofosbuvir for previously untreated chronic hepatitis C infection. N Engl J Med 2013; 368:1878-1887.
- Jacobson IM, et al. Sofosbuvir for hepatitis C genotype 2 or 3 in patients without treatment options. N Engl J Med 2013;368:1867-1877.