The FDA approved Gilead Sciences’ chronic hepatitis C virus (CHC) treatment Sovaldi™ (sofosbuvir) 400 mg tablets—the first drug that has shown the safety and efficacy to treat certain types of hepatitis C virus infection without the need for injection of interferon at the same time.

Solvadi is a once-daily oral nucleotide analog polymerase inhibitor designed to block a specific protein needed by the hepatitis C virus to replicate. Sovaldi is to be used as a component of a combination antiviral treatment regimen for CHC, which, depending on the patient’s type of infection, could combine the drug with ribavirin (RBV), or with ribavirin and peginterferon-alfa (RBV + peg-IFN).

“Today’s approval represents a significant shift in the treatment paradigm for some patients with chronic hepatitis C,” Edward Cox, M.D., director of the office of antimicrobial products in the FDA’s Center for Drug Evaluation and Research, said in an agency statement.

Solvadi was the second hepatitis C virus drug approved by the FDA in two weeks; the agency on November 22 approved Olysio (simeprevir), a treatment developed by Johnson & Johnson’s Janssen Pharmaceuticals unit.

While the AIDS Healthcare Foundation has criticized the price of Solvadi treatment—$84,000 for 12 weeks, $168,000 for 24 weeks—two Leerink Swann analysts said in a note to investors the cost was comparable to the other treatments, citing in part the $66,000, 12-week cost of Olysio, and $100,000 for an eight-week combination of Solvadi and Olysio.

“Given the pricing of alternative agents, we believe this does not pose a problem for future pricing of [a combination treatment of] Sovaldi/ledipasvir. We remain OP [outperform]-rated on GILD and expect a robust launch (starting Monday),” analysts Howard Liang, Ph.D., and Gena Wang, Ph.D., CFA, wrote in their note.

The FDA approved Solvadi on Friday, based primarily on results from four Phase III clinical trials that assessed the effects of 12 or 16 weeks of Sovaldi treatment combined with either RBV or the RBV/peg-IFN combination. Three studies evaluated Sovaldi plus RBV in genotype 2 (12-week treatment) or genotype 3 (24-week treatment) patients who were either treatment-naïve (FISSION), treatment-experienced (FUSION), or peg-IFN intolerant, ineligible, or unwilling (POSITRON). The fourth study, NEUTRINO, evaluated Sovaldi in combination with Peg-IFN/RBV in treatment naïve patients with genotypes 1, 4, 5, or 6.

All four showed Sovaldi-based therapy 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 (hepatitis C virus undetectable) 12 weeks after completing therapy (SVR12), at which point they are considered cured. Trial participants taking Sovaldi-based therapy achieved SVR12 rates of 50 to 90%.

Sovaldi won the FDA’s priority review and breakthrough therapy designations, which are granted to investigational medicines deemed to offer major advances in treatment over existing options.

On the basis of the drug’s breakthrough status, the FDA also considered data from two additional Phase III trials, VALENCE and PHOTON-1. In VALENCE, patients with genotype 3 hepatitis C infection were treated with Sovaldi and RBV for 24 weeks, with 84% of patients achieving SVR12. PHOTON-1 evaluated Sovaldi and RBV for 12 weeks in patients with genotype 2 hepatitis C infection co-infected with HIV-1 and for 24 weeks in patients with genotypes 1 or 3 hepatitis C co-infected with HIV-1. Trial participants achieved SVR12 rates of 76 to 92%.

In all, 1,947 patients were studied across all Phase III trials. The most common adverse events occurring in at least 20% of patients receiving Sovaldi in combination with Peg-IFN/RBV were fatigue, headache, nausea, insomnia, and anemia.

Sovaldi is also close to winning European Commission (EC) approval. On Novembe 22, the European Medicines Agency’s Committee for Medicinal Products for Human Use issued a positive opinion on the drug following an accelerated review procedure, reserved for medicinal products that are expected to be of major public health interest. If the EC approves Sovaldi as expected, the drug could be available in the European Union in the first quarter of 2014.

“It is our hope that Sovaldi will mark the beginning of a new era in hepatitis C treatment,” declared Gilead chairman and CEO John C. Martin, Ph.D.

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