EC grants marketing authorization for Gilead’s Epclusa for the treatment of all genotypes of chronic hepatitis C

Epclusa is the first and only all-oral, single tablet regimen for all genotypes (1-6) of chronic hepatitis C virus infection and is Gilead’s third Sofosbuvir-based treatment.

The combination of sofosbuvir and velpatasvir (SOF/VEL) for 12 weeks was authorized for use in patients without cirrhosis or with compensated cirrhosis (Child-Pugh A), and in combination with ribavirin (RBV) for patients with decompensated cirrhosis (Child-Pugh B or C). SOF/VEL is also the first single tablet regimen approved for the treatment of patients with HCV genotype 2 and 3, without the need for RBV. Physicians also have the flexibility to consider the addition of RBV for genotype 3 infected patients with compensated cirrhosis.

The Marketing Authorization follows an accelerated review procedure by the European Medicines Agency, reserved for medicinal products expected to be of major public health interest. It allows for the marketing of SOF/VEL in all 28 countries of the European Union (EU).

SOF/VEL is Gilead’s third sofosbuvir-based treatment to be granted Marketing Authorization by the European Commission for the treatment of chronic HCV infection. Sofosbuvir-based regimens are recommended by global guidelines across all HCV genotypes and disease severities. Today, nearly one million patients worldwide have been prescribed a sofosbuvir-based regimen.

“Built on the foundation of sofosbuvir, SOF/VEL offers a highly effective and tolerable choice which is protease inhibitor free and ribavirin free for the majority of patients. For the first time we have a once-daily single tablet treatment option which works across all genotypes including genotype 3, which is often the least responsive to treatment,” said Professor Stefan Zeuzem, Professor of Medicine and Chief of the Department of Medicine at the J.W. Goethe University Hospital, Frankfurt, Germany and an ASTRAL-1, 2 and 3 study investigator. “This approval marks a significant advance in the treatment of HCV and is an important step in our efforts to achieve elimination of the disease throughout Europe.”

The authorization of SOF/VEL is supported by data from four Phase III studies, ASTRAL-1, ASTRAL-2, ASTRAL-3 and ASTRAL-4. In the ASTRAL-1, ASTRAL-2 and ASTRAL-3 studies, 1,035 patients with genotypes 1-6 HCV infection, without cirrhosis or with compensated cirrhosis (Child-Pugh A) received 12 weeks of SOF/VEL. The ASTRAL-4 study randomized 267 patients with genotypes 1-6 HCV infection, with decompensated cirrhosis (Child-Pugh B) to receive 12 weeks of SOF/VEL with or without RBV or 24 weeks of SOF/VEL alone. The primary endpoint for all studies was the sustained viral response rate 12 weeks after treatment (SVR12).

John Milligan, President and CEO of Gilead said: “The burden of hepatitis C across Europe is substantial and growing rapidly with approximately 15 million people chronically infected. The European approval of SOF/VEL reflects our continued focus to bring a cure to all infected patients across the region and we look forward to working with physicians, healthcare providers and governments to make it available as quickly as possible.”

Of the 1,035 patients treated with SOF/VEL for 12 weeks in the ASTRAL-1, ASTRAL-2 and ASTRAL-3 studies, 1,015 (98%) achieved SVR12. In ASTRAL-4, patients with decompensated cirrhosis receiving SOF/VEL with RBV for 12 weeks achieved a higher SVR12 rate (94%) compared to those who received SOF/VEL for 12 weeks or 24 weeks without RBV (83% and 86%, respectively.) The most common adverse events in the four ASTRAL studies were headache, fatigue and nausea, and were comparable in incidence to the placebo group included in ASTRAL-1.

Sofosbuvir as a single agent was granted marketing authorization in the EU on 16 January 2014 under the trade name Sovaldi. The fixed-dose combination of sofosbuvir (400 mg) and ledipasvir (90 mg) received marketing authorization in the EU on 18 November 2014 under the trade name Harvoni.

Epclusa was approved by the FDA on 28 June 2016 for the treatment of adults with genotype 1-6 chronic HCV infection.