FDA approves Epclusa for treatment of chronic Hepatitis C virus infection

The U.S. Food and Drug Administration approved Epclusa to treat adult patients with chronic hepatitis C virus (HCV) both with and without cirrhosis (advanced liver disease). For patients with moderate to severe cirrhosis (decompensated cirrhosis), Epclusa is approved for use in combination with the drug ribavirin. Epclusa is a fixed-dose combination tablet containing sofosbuvir, a drug approved in 2013, and velpatasvir, a new drug, and is the first to treat all six major forms of HCV.

“This approval offers a management and treatment option for a wider scope of patients with chronic hepatitis C,” said Edward Cox, M.D., director of the Office of Antimicrobial Products in the FDA’s Center for Drug Evaluation and Research.

Hepatitis C is a viral disease that causes inflammation of the liver that can lead to diminished liver function or liver failure. There are at least six distinct HCV genotypes, or strains, which are genetically distinct groups of the virus. Knowing the genotype helps inform treatment recommendations and the duration of treatment. Approximately 75 percent of Americans with HCV have genotype 1; 20-25 percent have genotypes 2 or 3; and a small numbers of patients are infected with genotypes 4, 5 or 6. According to the Centers for Disease Control and Prevention, HCV infection becomes chronic in approximately 75 to 85 percent of cases. Patients who suffer from chronic HCV infection over many years may have complications, such as bleeding, jaundice (yellowish eyes or skin), fluid accumulation in the abdomen, infections, liver cancer and death.

The safety and efficacy of Epclusa for 12 weeks was evaluated in three Phase III clinical trials of 1,558 subjects without cirrhosis or with compensated cirrhosis (mild cirrhosis). Results demonstrated that 95–99 percent of patients who received Epclusa had no virus detected in the blood 12 weeks after finishing treatment, suggesting the patients’ infections had been cured. The safety and efficacy of Epclusa was also evaluated in a clinical trial of 267 subjects with decompensated cirrhosis (moderate to severe cirrhosis), of whom 87 subjects received Epclusa in combination with ribavirin for 12 weeks, and 94 percent of these patients had no virus detected in the blood 12 weeks after finishing treatment.

The most common side effects of Epclusa include headache and fatigue. Epclusa and ribavirin combination regimens are contraindicated for patients for whom ribavirin is contraindicated.

Epclusa 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 Epclusa is not recommended. Epclusa also carries a warning not to use with certain drugs that may reduce the amount of Epclusa in the blood which could lead to reduced efficacy of Epclusa.

Epclusa was reviewed under the FDA’s priority review program, which provides for an expedited review of drugs that treat serious conditions and, if approved, would provide significant improvement in safety or effectiveness.

Epclusa is manufactured and marketed by Gilead Sciences, Inc., of Foster City, California.

The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency is also responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.

FDA approves vaccine to prevent cholera for travelers

The U.S. Food and Drug Administration today approved Vaxchora, a vaccine for the prevention of cholera caused by serogroup O1 in adults 18 through 64 years of age traveling to cholera-affected areas. Vaxchora is the only FDA-approved vaccine for the prevention of cholera.

Cholera, a disease caused by Vibrio cholerae bacteria, is acquired by ingesting contaminated water or food and causes a watery diarrhea that can range from mild to extremely severe. Often the infection is mild; however, severe cholera is characterized by profuse diarrhea and vomiting, leading to dehydration. It is potentially life threatening if treatment with antibiotics and fluid replacement is not initiated promptly. According to the World Health Organization, serogroup O1 is the predominant cause of cholera globally.

“The approval of Vaxchora represents a significant addition to the cholera-prevention measures currently recommended by the Centers for Disease Control and Prevention for travelers to cholera-affected regions,” said Peter Marks, M.D., Ph.D., director of the FDA’s Center for Biologics Evaluation and Research.

While cholera is rare in the U.S., travelers to parts of the world with inadequate water and sewage treatment and poor sanitation are at risk for infection. Travelers to cholera-affected areas have relied on preventive strategies recommended by the CDC to protect themselves against cholera, including safe food and water practices and frequent hand washing.

Vaxchora is a live, weakened vaccine that is taken as a single, oral liquid dose of approximately three fluid ounces at least 10 days before travel to a cholera-affected area.

Vaxchora’s efficacy was demonstrated in a randomized, placebo-controlled human challenge study of 197 U.S. volunteers from 18 through 45 years of age. Of the 197 volunteers, 68 Vaxchora recipients and 66 placebo recipients were challenged by oral ingestion of Vibrio cholerae, the bacterium that causes cholera. Vaxchora efficacy was 90 percent among those challenged 10 days after vaccination and 80 percent among those challenged three months after vaccination.  The study included provisions for administration of antibiotics and fluid replacement in symptomatic participants. To prevent transmission of cholera into the community, the study included provisions for administration of antibiotics to participants not developing symptoms.

Two placebo-controlled studies to assess the immune system’s response to the vaccine were also conducted in the U.S. and Australia in adults 18 through 64 years of age. In the 18 through 45 year age group, 93 percent of Vaxchora recipients produced antibodies indicative of protection against cholera. In the 46 through 64 years age group, 90 percent produced antibodies indicative of protection against cholera. The effectiveness of Vaxchora has not been established in persons living in cholera-affected areas.

The safety of Vaxchora was evaluated in adults 18 through 64 years of age in four randomized, placebo-controlled, multicenter clinical trials; 3,235 study participants received Vaxchora and 562 received a placebo. The most common adverse reactions reported by Vaxchora recipients were tiredness, headache, abdominal pain, nausea/vomiting, lack of appetite and diarrhea.

The FDA granted the Vaxchora application fast track designation andpriority review status. These are distinct programs intended to facilitate and expedite the development and review of medical products that address a serious or life-threatening condition. In addition, the FDA awarded the manufacturer of Vaxchora a tropical disease priority review voucher, under a provision included in the Food and Drug Administration Amendments Act of 2007. This provision aims to encourage the development of new drugs and biological products for the prevention and treatment of certain tropical diseases.

Vaxchora is manufactured by PaxVax Bermuda Ltd., located in Hamilton, Bermuda.

The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.