FDA Approves Gilead's Epclusa Combo Pill for All Hepatitis C Genotypes


On June 28 the U.S. Food and Drug Administration (FDA) approved Gilead Sciences Epclusa, a new once-daily combination pill containing sofosbuvir and velpatasvir, for the treatment of adults with hepatitis C virus (HCV) genotypes 1 through 6 -- the first approved oral pangenotypic regimen. While it is more effective against more types of HCV, Epclusa will cost less than most earlier interferon-free direct-acting antiviral regimens.

Epclusa contains 400 mg of the nucleotide HCV polymerase inhibitor sofosbuvir (marketed separately as Sovaldi) and 100 mg of the novel NS5A inhibitor velpatasvir.

Unlike the currently available Harvoni (sofosbuvir/ledipasvir) combination, which is indicated for HCV genotypes 1, 4, and the little-studied 5 and 6, Epclusa is active against all genotypes. Genotype 1 -- the predominant type in the U.S. and Europe -- now has several good treatment options available. Other genotypes are more common elsewhere, including genotype 3 in India, genotype 4 in the Middle East and North Africa, genotype 5 in South Africa, and genotype 6 in parts of Asia. Pangenotypic regimens are especially welcome in low- and middle-income countries that have high burdens of hepatitis C, as they can be used without prior genotypic testing.

Epclusa is a complete single-tablet regimen that can be used without ribavirin for all HCV genotypes. It was approved for previously untreated and treatment-experienced adult chronic hepatitis C patients with or without cirrhosis. However, people with decompensated cirrhosis (Child-Pugh B or C) should add ribavirin. Treatment duration is 12 weeks for all patients. Epclusa should not be used with certain other medications (including amiodarone, rifampin, St. John’s wort, and carbamazepine) due to the risk of drug-drug interactions that could cause side effects or reduce drug concentrations.

Epclusa is approved to treat people with HIV and HCV coinfection. However, it should not be used with some antiretrovirals -- including efavirenz and tipranavir -- and people taking tenofovir should have their kidney function monitored regularly.

Epclusa was approved based on clinical trials showing that it produces high rates of sustained virological response (SVR), considered to be a cure. In the Phase 3 ASTRAL trials sofosbuvir/velpatasvir cured 99% of chronic hepatitis C patients with genotypes 1, 2, 4, 5, and 6, and 95% of those with harder-to-treat genotype 3. SVR rates were similar regardless of prior treatment experience or the presence of compensated cirrhosis. For people with decompensated cirrhosis, 94% achieved SVR with sofosbuvir/velpatasvir plus ribavirin in ASTRAL-4. ASTRAL-5 showed a cure rate of 95% for HIV/HCV coinfected people. Treatment was safe and generally well-tolerated, with few serious drug-related adverse events or drug discontinuations. The most commonly reported side effects include headache and fatigue.

"The approval of Epclusa represents an important step forward in the global effort to control and potentially eliminate HCV as it provides a safe, simple and effective cure for the majority of HCV-infected patients, regardless of genotype," trial investigator Ira Jacobson from Mount Sinai Beth Israel said in a Gilead press release. "Building on the established backbone of sofosbuvir, Epclusa demonstrated consistently high cure rates across all genotypes, including among patients with genotype 2 and 3, who traditionally have required ribavirin or other multi-pill regimens."

Gilead set the list price of Epclusa at $74,760 -- lower than the retail cost of its earlier Sovaldi ($84,000) and Harvoni ($94,500), not to mention a combination of Sovaldi plus Bristol-Myers Squibb's $63,000 daclatasvir (Daklinza). The only regimen with a lower list price is Merck's grazoprevir/elbasvir (Zepatier), at $54,600, which is only indicated for genotypes 1 and 4.

At this price point and given the good tolerability of velpatasvir, there appears to be no reason not to use Epclusa rather than sofosbuvir alone for genotype 2, or sofosbuvir plus daclatasvir or pegylated interferon/ribavirin for genotype 3. However, Harvoni is likely to remain the preferred regimen for treatment-naive genotype 1 patients without cirrhosis, who can usually be cured in just 8 weeks -- a shorter-duration option that is not FDA-approved for Epclusa.

To assist eligible patients in the U.S., Gilead has added Epclusa to its patient assistance and co-pay programs (www.MySupportPath.com).

Gilead notes that it is working with regional business partners, generic licensing partners, the Medicines Patent Pool, and other stakeholders to expand treatment access worldwide. Epclusa has already been licensed to 11 manufacturing partners in India that can now begin producing and distributing a generic version of sofosbuvir/velpatasvir for 101 low-income countries.



FDA. FDA approves Epclusa for treatment of chronic Hepatitis C virus infection. Press release. June 28, 2016.

Gilead Sciences. U.S. Food and Drug Administration Approves Gilead’s Epclusa (Sofosbuvir/Velpatasvir) for the Treatment of All Genotypes of Chronic Hepatitis C. Press release. June 28, 2016.