Gil Roth12.09.13
Gilead Sciences has received approval from the FDA for Sovaldi (sofosbuvir) 400 mg tablets, a once-daily oral nucleotide analog polymerase inhibitor for the treatment of chronic hepatitis C (CHC) infection as a component of a combination antiviral treatment regimen. The FDA granted Sovaldi Priority Review and Breakthrough Therapy designation, which is granted to investigational medicines that may offer major advances in treatment over existing options.
Sovaldi’s efficacy has been established in subjects with hepatitis C virus (HCV) genotypes 1, 2, 3 or 4 infection, including those with hepatocellular carcinoma meeting Milan criteria (awaiting liver transplantation) and those with HCV/HIV-1 co-infection. Treatment regimen, duration and response to Sovaldi are dependent on viral genotype and patient population, and associated baseline factors. Monotherapy is not recommended.
Sovaldi’s approval is supported primarily by data from four Phase III studies, which evaluated 12 or 16 weeks of treatment with Sovaldi combined with either ribavirin (RBV) or RBV plus pegylated interferon (peg-IFN). Three of these studies evaluated Sovaldi plus RBV in genotype 2 or 3 patients who were either treatment-naïve, treatment-experienced or peg-IFN intolerant, ineligible or unwilling. The fourth trial evaluated Sovaldi in combination with Peg-IFN/RBV in treatment-naïve patients with genotypes 1, 4, 5 or 6. In these studies, Sovaldi-based therapy was found to be superior to historical controls or to placebo, or non-inferior to currently available treatment options based on the proportion of patients who had a sustained virologic response (HCV undetectable) 12 weeks after completing therapy (SVR12). Patients who achieve SVR12 are considered cured of HCV. Trial participants taking Sovaldi-based therapy achieved SVR12 rates of 50-90%.
During the FDA’s review, data from two additional Phase III studies were added to the NDA as a result of the Breakthrough Designation status. One study had patients with genotype 3 HCV infection were treated with Sovaldi and RBV for 24 weeks. Eighty-four percent of patients in this trial achieved SVR12. The other study evaluated Sovaldi and RBV for 12 weeks in patients with genotype 2 HCV infection co-infected with HIV-1 and for 24 weeks in patients with genotypes 1 or 3 HCV co-infected with HIV-1. Trial participants achieved SVR12 rates of 76-92%. In all Phase III studies of Sovaldi, no viral resistance to the drug was detected among patients who relapsed following completion of therapy.
To date, nearly 3,000 patients have received at least one dose of Sovaldi in Phase II or III studies. Sovaldi combination therapy was well tolerated in clinical studies. Adverse events were generally mild and there were few treatment discontinuations due to adverse events, according to Gilead.
On November 22, 2013, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) issued a positive opinion on Gilead’s application for marketing authorization for Sovaldi. The CHMP opinion was adopted following an accelerated review procedure, which is reserved for medicinal products that are expected to be of major public health interest. This assessment does not guarantee marketing authorization by the European Commission. If approved, Sovaldi could be available in the European Union in the 1Q14. Applications for marketing approval of Sovaldi are also pending in Australia, Canada, New Zealand, Switzerland and Turkey.