Gilead Sciences has announced that the US Food and Drug Administration (FDA) has approved Sovaldi (sofosbuvir) 400mg 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.
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.
Sovaldi in combination with ribavirin for 24 weeks can be considered for CHC patients with genotype 1 infection who are interferon ineligible. Additionally, Sovaldi should be used in combination with ribavirin for treatment of CHC patients with hepatocellular carcinoma awaiting liver transplantation for up to 48 weeks or until liver transplantation to prevent post-transplant HCV infection.
Treatment regimen, duration and response to Sovaldi are dependent on viral genotype and patient population, and associated baseline factors. Monotherapy is not recommended.
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.
Gilead Sciences chairman and CEO Dr John C Martin noted it is the company's hope that Sovaldi will mark the beginning of a new era in hepatitis C treatment.
"Gilead is proud to have played a role in bringing about this important therapeutic advance and we would like to extend our thanks to the many patients and physicians who partnered with us on Sovaldi's clinical studies," Dr Martin added.
Sovaldi's approval is supported primarily by data from four Phase III studies, NEUTRINO, FISSION, POSITRON and FUSION, which evaluated 12 or 16 weeks of treatment with Sovaldi combined with either RBV or RBV plus peg-IFN.
Three of these studies evaluated Sovaldi plus RBV in genotype 2 or 3 patients who were either treatment-naive (FISSION), treatment-experienced (FUSION) or peg-IFN intolerant, ineligible or unwilling (POSITRON).
NEUTRINO evaluated Sovaldi in combination with Peg-IFN/RBV in treatment naive patients with genotypes 1, 4, 5 or 6. In these studies, Sovaldi-based therapy was found to be superior to historical controls (NEUTRINO and FUSION) or to placebo (POSITRON), or non-inferior to currently available treatment options (FISSION) 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 percent. For full study details, see the Clinical Studies section of the full Prescribing Information.
During the FDA's review, data from two additional Phase III studies, VALENCE and PHOTON-1, were added to the NDA as a result of the breakthrough designation status. In the VALENCE study, patients with genotype 3 HCV infection were treated with Sovaldi and RBV for 24 weeks.
According to the company, 84% of patients in this trial achieved SVR12. The PHOTON-1 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 percent. In all Phase 3 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 2 or 3 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.
The most common adverse events occurring in at least 20 percent of patients receiving Sovaldi in combination with Peg-IFN/RBV were fatigue, headache, nausea, insomnia and anemia.
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 first quarter of 2014. Applications for marketing approval of Sovaldi are also pending in Australia, Canada, New Zealand, Switzerland and Turkey.
Dr Jacobson is a paid consultant to Gilead.
The wholesaler acquisition cost of a 28-tablet bottle of Sovaldi in the US is $28,000.