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FDA approves Epclusa for all HCV genotypes

The FDA announced it has approved Epclusa for the treatment of all chronic hepatitis C virus genotypes in adults with and without cirrhosis. For patients with moderate to severe cirrhosis, it is approved in combination with ribavirin.

Epclusa (sofosbuvir/velpatasvir, Gilead Sciences), a pangenotypic, once-daily tablet containing 400 mg of sofosbuvir and 100 mg of velpatasvir, is the first combination drug to treat all six major forms of HCV.

“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,” Ira Jacobson, MD, chairman of the department of medicine at Mount Sinai Beth Israel, New York City, principal investigator in the Epclusa clinical trials and HCV Next Co-Chief Medical Editor, said in a press release from Gilead Sciences. “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.”

Ira Jacobson, MD

Ira Jacobson

According to a press release from Gilead Sciences, the approval is indicative of positive results from multiple phase 3 studies — ASTRAL-1, ASTRAL-2, ASTRAL-3 and ASTRAL-4. The results demonstrated between 95% and 99% of all patients who received sofosbuvir/velpatasvir had undetectable virus in their blood 12 weeks post-treatment. The FDA stated in their release that this suggests the patients’ infection had been cured.

In the ASTRAL-1, ASTRAL-2 and ASTRAL-3 trials, 1,035 patients underwent therapy with the fixed combination regimen for 12 weeks. Of these patients, 98% achieved SVR at 12 weeks (n = 1,015). In the ASTRAL-4 trial, researchers randomly assigned 267 patients with decompensated cirrhosis to receive either sofosbuvir/velpatasvir with or without ribavirin for 12 weeks or 24 weeks of sofosbuvir/velpatasvir. Ninety-four percent of patients who received sofosbuvir/velpatasvir plus ribavirin for 12 weeks achieved SVR12, whereas 83% of patients who received sofosbuvir/velpatasvir for 12 weeks achieved SVR12 and 86% of patients who received sofosbuvir/velpatasvir for 24 weeks achieved SVR.

The safety and efficacy of sofosbuvir/velpatasvir was evaluated in an additional clinical trial of 267 patients with decompensated cirrhosis, of which 87 patients received sofosbuvir/velpatasvir in combination with ribavirin for 12 weeks, and 94% of them had no virus detected in the blood 12 weeks post-treatment.

“This approval offers a management and treatment option for a wider scope of patients with chronic hepatitis C,” Edward Cox, MD, director of the office of antimicrobial products in the FDA’s Center for Drug Evaluation and Research, said in a press release.

According to the FDA, the most common adverse events include headache and fatigue, and sofosbuvir/velpatasvir plus ribavirin are contraindicated for patients for whom ribavirin is contraindicated.

The FDA also noted that sofosbuvir/velpatasvir carries a warning for patients and health care providers that serious slowing of the heart rate (symptomatic bradycardia) and cases requiring pacemaker intervention have been reported when amiodarone is used with sofosbuvir in combination with another HCV direct-acting antiviral. Co-administration of amiodarone with sofosbuvir/velpatasvir is not recommended. Sofosbuvir/velpatasvir also carries a warning not to use with certain drugs that may reduce the amount of sofosbuvir/velpatasvir in the blood which could lead to reduced efficacy of the medication.

According to Gilead spokesperson Cara Miller, Gilead is planning on shipping the medication to wholesalers by the end of the week at a wholesale acquisition cost of $74,760.

“Gilead believes the pricing of Epclusa will facilitate access for the U.S. population with the greatest unmet medical need — patients with genotypes 2 and 3 who previously required more complex and costly multi-tablet regimens. For genotype 3 patients in particular, the cost of Epclusa will be half the cost of the most commonly used regimen (sofosbuvir plus daclatasvir),” Miller said via email. 

The FDA granted priority review designation for sofosbuvir/velpatasvir in January.

The European Committee for Medicinal Products for Human Use granted a positive opinion for Gilead Science’s Marketing Authorization Application for Epclusa in May.

Disclosure: Cox is employed by the FDA. Jacobson reports various financial relationships with AbbVie, Achillion, Alnylam, Bristol-Myers Squibb, Enanta, Gilead Sciences, Janssen Therapeutics, Merck and Tobira.

The FDA announced it has approved Epclusa for the treatment of all chronic hepatitis C virus genotypes in adults with and without cirrhosis. For patients with moderate to severe cirrhosis, it is approved in combination with ribavirin.

Epclusa (sofosbuvir/velpatasvir, Gilead Sciences), a pangenotypic, once-daily tablet containing 400 mg of sofosbuvir and 100 mg of velpatasvir, is the first combination drug to treat all six major forms of HCV.

“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,” Ira Jacobson, MD, chairman of the department of medicine at Mount Sinai Beth Israel, New York City, principal investigator in the Epclusa clinical trials and HCV Next Co-Chief Medical Editor, said in a press release from Gilead Sciences. “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.”

Ira Jacobson, MD

Ira Jacobson

According to a press release from Gilead Sciences, the approval is indicative of positive results from multiple phase 3 studies — ASTRAL-1, ASTRAL-2, ASTRAL-3 and ASTRAL-4. The results demonstrated between 95% and 99% of all patients who received sofosbuvir/velpatasvir had undetectable virus in their blood 12 weeks post-treatment. The FDA stated in their release that this suggests the patients’ infection had been cured.

In the ASTRAL-1, ASTRAL-2 and ASTRAL-3 trials, 1,035 patients underwent therapy with the fixed combination regimen for 12 weeks. Of these patients, 98% achieved SVR at 12 weeks (n = 1,015). In the ASTRAL-4 trial, researchers randomly assigned 267 patients with decompensated cirrhosis to receive either sofosbuvir/velpatasvir with or without ribavirin for 12 weeks or 24 weeks of sofosbuvir/velpatasvir. Ninety-four percent of patients who received sofosbuvir/velpatasvir plus ribavirin for 12 weeks achieved SVR12, whereas 83% of patients who received sofosbuvir/velpatasvir for 12 weeks achieved SVR12 and 86% of patients who received sofosbuvir/velpatasvir for 24 weeks achieved SVR.

The safety and efficacy of sofosbuvir/velpatasvir was evaluated in an additional clinical trial of 267 patients with decompensated cirrhosis, of which 87 patients received sofosbuvir/velpatasvir in combination with ribavirin for 12 weeks, and 94% of them had no virus detected in the blood 12 weeks post-treatment.

“This approval offers a management and treatment option for a wider scope of patients with chronic hepatitis C,” Edward Cox, MD, director of the office of antimicrobial products in the FDA’s Center for Drug Evaluation and Research, said in a press release.

According to the FDA, the most common adverse events include headache and fatigue, and sofosbuvir/velpatasvir plus ribavirin are contraindicated for patients for whom ribavirin is contraindicated.

The FDA also noted that sofosbuvir/velpatasvir carries a warning for patients and health care providers that serious slowing of the heart rate (symptomatic bradycardia) and cases requiring pacemaker intervention have been reported when amiodarone is used with sofosbuvir in combination with another HCV direct-acting antiviral. Co-administration of amiodarone with sofosbuvir/velpatasvir is not recommended. Sofosbuvir/velpatasvir also carries a warning not to use with certain drugs that may reduce the amount of sofosbuvir/velpatasvir in the blood which could lead to reduced efficacy of the medication.

According to Gilead spokesperson Cara Miller, Gilead is planning on shipping the medication to wholesalers by the end of the week at a wholesale acquisition cost of $74,760.

“Gilead believes the pricing of Epclusa will facilitate access for the U.S. population with the greatest unmet medical need — patients with genotypes 2 and 3 who previously required more complex and costly multi-tablet regimens. For genotype 3 patients in particular, the cost of Epclusa will be half the cost of the most commonly used regimen (sofosbuvir plus daclatasvir),” Miller said via email. 

The FDA granted priority review designation for sofosbuvir/velpatasvir in January.

The European Committee for Medicinal Products for Human Use granted a positive opinion for Gilead Science’s Marketing Authorization Application for Epclusa in May.

Disclosure: Cox is employed by the FDA. Jacobson reports various financial relationships with AbbVie, Achillion, Alnylam, Bristol-Myers Squibb, Enanta, Gilead Sciences, Janssen Therapeutics, Merck and Tobira.

    Perspective

    Michael S. Saag

    It is heartening to see the speed and quality of the advances in the treatment of hepatitis C in the last two years. Our challenge now is to implement treatment to the millions of people around the world with a goal of eradicating HCV. A key barrier to eradication is the cost of the medicines. Merck launched their product in January at a substantial reduction from previous list prices of drugs ($54,000); Gilead has launched their new combination at $75,000, which is less than their previous product (sofosbuvir/ledipasvir; Harvoni at $90,000).

    We are making progress, but the prices still must come down further if we can truly afford the cost of eradication.

    • Michael S. Saag, MD
    • Co-Chief Medical Editor, HCV Next
      Professor of medicine, Jim Straley Chair in AIDS Research, director of the Center for AIDS Research
      University of Alabama at Birmingham

    Disclosures: Saag reports no relevant financial disclosures.

    Perspective

    Zobair M. Younossi

    Hepatitis C virus causes a systemic disease with both hepatic (eg, cirrhosis, liver cancer) and extrahepatic (eg, cryoglobulinemia, severe chronic fatigue) manifestations affecting 130 million to 150 million individuals globally. HCV infection has a negative impact on clinical and patient-reported outcomes (PROs) as well as causing tremendous economic burden to society. In the recent past, treatment of HCV has been revolutionized with the development of treatment regimens that are highly effective and well tolerated.

    The recent FDA approval of Epclusa (sofosbuvir/velpatasvir, Gilead Sciences) provides an additional important advance for treating HCV infection. This pangenotypic fixed-dose regimen can be given to any HCV patient who does not have evidence of hepatic decompensation for 12 weeks with a sustained virologic response rate of 98%. Even for the difficult-to-treat HCV patients who have decompensated cirrhosis, Epclusa plus ribavirin for 12 weeks can provide an SVR rate of 94%. These regimens are well tolerated without any additional side effects.

    In addition to achieving the high SVR rates, these regimens are associated with improvement of PROs (eg, quality of life and fatigue) during treatment and after achieving SVR. Although economic analysis of this specific regimen currently does not exist, other similar regimens have been shown to be cost-effective and provide long-term economic benefit to the society.

    In my view, in 2016, curing HCV is no longer a challenge. In fact, with these treatments, we have the access to the regimens that can eradicate HCV from the United States. Nevertheless, our current challenge related to HCV is to identify all infected patients through effective screening programs and linking the infected patients to appropriate care and treatment. In this context, there is a need for national policy that should include the perspective of all important stakeholders (ie, patients, providers, payers, pharmaceutical companies and policy makers) to develop a 10-year plan to eradicate HCV from the United States. Given the clinical, PRO and economic burden of HCV and the availability of these highly effective regimens, we can certainly accomplish the goal of eradication of HCV. For this, we need a “national will” and a national strategy to eradicate HCV and take advantage of the advances from the “golden age” of HCV treatment.

    • Zobair M. Younossi, MD, MPH, FACG, AGAF, FAASLD
    • Chairman, Department of Medicine, Inova Fairfax Hospital
      Vice President for Research, Inova Health System
      Professor of Medicine, VCU-Inova Campus
      Beatty Center for Integrated Research

    Disclosures: Younossi reports consulting for AbbVie, Bristol-Myers Squibb, Gilead and Intercept, and serving on advisory committees or review panels for AbbVie and Bristol-Myers Squibb.