FDA panel unanimously approves simeprevir for HCV genotype 1

  • October 24, 2013

The FDA’s Antiviral Drugs Advisory Committee today voted that available data overwhelmingly supports approval of simeprevir in combination with pegylated interferon and ribavirin for treatment of hepatitis C genotype 1 infections.

The panel voted 19-0 with no abstentions after researchers presented study results demonstrating the once-daily protease inhibitor pill manufactured by Janssen Pharmaceuticals, a Johnson & Johnson company, was superior to placebo in achieving a sustained virologic response (SVR) in treatment-naive patients with HCV and those who relapsed after prior pegylated interferon and ribavirin (PR) therapy.

“I thought the evidence was pretty overwhelming,” committee member Dean Follmann, PhD, chief, biostatistics research branch, National Institute of Allergy and Infectious Diseases, said. “It was probably the easiest vote I ever had.”

Presenters provided safety and efficacy details from four double-blind, placebo-controlled studies — two phase 3 studies on treatment-naive patients, one phase 3 study on prior relapsers and one phase 2b study on prior relapsers and nonresponders.

The studies demonstrated positive SVR results in most cases, but a subpopulation of HCV patients — those with genotype 1a and a Q80K polymorphism — responded similarly to controls in naive or relapse trials.

Due to the reduction in efficacy apparent in these subjects, the FDA’s Division of Antiviral Products stated it intends to recommend screening all genotype 1a subjects for the Q80K viral polymorphism before beginning simeprevir with PR therapy in order to potentially consider alternative treatment options.

During discussion of the proposal, the panel voiced questions over whether it was enough to suggest physicians “consider” alternative treatment as opposed to “recommending” another treatment.

The panel also discussed aspects of simeprevir’s safety profile and agreed without a vote that a recommendation for sun-protection measures should be included with the warnings and precautions section of simeprevir’s prescribing information because of photosensitivity reactions during clinical trials.

Additional skin reactions during clinical trials also prompted discussions of whether skin rash should be included in the warnings and precautions section. The question arose because of apparent differences between presentation and management strategy for rash and photosensitivity.

“There are varying opinions about what should be on the label in what sections,” Committee Chairman Yoshihiko Murata, MD, PhD, division of infectious diseases, University of Rochester School of Medicine and Dentistry, said in summarizing the discussion. No final vote was conducted on the discussion point.

The panel also advised that further postmarketing studies should be conducted to better define potential risks to several portions of the population and means to optimize use of simeprevir.

A final decision by the FDA is expected next month.

On Friday, the panel will hear details regarding sofosbuvir (Gilead Sciences).

An FDA background report on sofosbuvir concluded that adding the medication to standard drug therapy cured 90% of those with HCV genotypes 1, 4, 5 and 6 during a 12-week period.

Healio.com/Hepatology will cover the meeting.