FDA advisory panel decisions

Panel recommends FDA approve sofosbuvir for hepatitis C

The FDA’s Antiviral Drugs Advisory Committee today recommended approval of sofosbuvir, a first-in-class, once-daily oral nucleotide inhibitor from Gilead Sciences, for treatment of chronic hepatitis C virus genotypes 1, 2, 3 and 4.

The panel voted unanimously and enthusiastically in support of approving sofosbuvir in combination with ribavirin for treatment of HCV GT 2 and 3 in adult patients.

“This is a game-changer,” committee member Marc G. Ghany, MD, MHSc, staff physician with the liver diseases branch of the National Institute of Diabetes and Digestive and Kidney Diseases, said.

The panel also voted 15-0 but offered more reservations in support of approving sofosbuvir in combination with pegylated interferon and ribavirin (PR) for treatment of HCV GT 1 and 4 in treatment-naive patients.

“I was hesitant to give approval for a one-arm study,” committee member Dean Follmann, PhD, chief, biostatistics research branch, National Institute of Allergy and Infectious Diseases, said. “The 90% success rate is what really made me comfortable with this.”

The votes followed a discussion on a series of phase 3 studies of a sofosbuvir-based regimen, generally of 12 to 16 weeks, that demonstrated similar or superior effectiveness to current treatment options at primary endpoint of sustained virologic response (SVR) at 12 weeks.

The committee also discussed, but did not vote, on whether evidence supported sofosbuvir in combination with PR for treatment of chronic hepatitis C in patients with GT 1 infection who are nonresponders to a prior course of PR.

Studies did not directly analyze this patient population, but the FDA presented extrapolated data that suggested about 75% of treatment-experienced patients might respond positively to the therapy.

Several committee members expressed concern over the lack of real data, while others suggested it was a risk worth taking.

Thomas P. Giordano, MD, MPH, associate professor of medicine at Baylor College of Medicine, questioned whether voicing approval was appropriate.

“Clinicians are going to do what they have to do to take care of their patients, but the agency’s responsibility is at a different level,” he said.

On the discussion of whether evidence supported use of sofosbuvir in combination with ribavirin in hepatocellular carcinoma patients meeting Milan criteria awaiting liver transplantation, panel Chairman Yoshihiko Murata, MD, PhD, division of infectious diseases, University of Rochester School of Medicine and Dentistry, said there was a consensus among the panel on the need to treat this population.

“It’s work in progress, but it’s work that has to be done,” Donald J. Alcendor, PhD, associate professor, department of microbiology  and immunology at Meharry Medical College, said.

The FDA’s Antiviral Drugs Advisory Committee today recommended approval of sofosbuvir, a first-in-class, once-daily oral nucleotide inhibitor from Gilead Sciences, for treatment of chronic hepatitis C virus genotypes 1, 2, 3 and 4.

The panel voted unanimously and enthusiastically in support of approving sofosbuvir in combination with ribavirin for treatment of HCV GT 2 and 3 in adult patients.

“This is a game-changer,” committee member Marc G. Ghany, MD, MHSc, staff physician with the liver diseases branch of the National Institute of Diabetes and Digestive and Kidney Diseases, said.

The panel also voted 15-0 but offered more reservations in support of approving sofosbuvir in combination with pegylated interferon and ribavirin (PR) for treatment of HCV GT 1 and 4 in treatment-naive patients.

“I was hesitant to give approval for a one-arm study,” committee member Dean Follmann, PhD, chief, biostatistics research branch, National Institute of Allergy and Infectious Diseases, said. “The 90% success rate is what really made me comfortable with this.”

The votes followed a discussion on a series of phase 3 studies of a sofosbuvir-based regimen, generally of 12 to 16 weeks, that demonstrated similar or superior effectiveness to current treatment options at primary endpoint of sustained virologic response (SVR) at 12 weeks.

The committee also discussed, but did not vote, on whether evidence supported sofosbuvir in combination with PR for treatment of chronic hepatitis C in patients with GT 1 infection who are nonresponders to a prior course of PR.

Studies did not directly analyze this patient population, but the FDA presented extrapolated data that suggested about 75% of treatment-experienced patients might respond positively to the therapy.

Several committee members expressed concern over the lack of real data, while others suggested it was a risk worth taking.

Thomas P. Giordano, MD, MPH, associate professor of medicine at Baylor College of Medicine, questioned whether voicing approval was appropriate.

“Clinicians are going to do what they have to do to take care of their patients, but the agency’s responsibility is at a different level,” he said.

On the discussion of whether evidence supported use of sofosbuvir in combination with ribavirin in hepatocellular carcinoma patients meeting Milan criteria awaiting liver transplantation, panel Chairman Yoshihiko Murata, MD, PhD, division of infectious diseases, University of Rochester School of Medicine and Dentistry, said there was a consensus among the panel on the need to treat this population.

“It’s work in progress, but it’s work that has to be done,” Donald J. Alcendor, PhD, associate professor, department of microbiology  and immunology at Meharry Medical College, said.

    See more from Hepatitis C Resource Center