FDA approves Zepatier for HCV genotypes 1, 4

HIV and Hepatitis Article

January 29, 2016

Merck announced the FDA has approved Zepatier for the treatment of adult patients with chronic hepatitis C virus genotype 1 and 4 infection, with or without ribavirin.

Zepatier (grazoprevir/elbasvir, Merck), a once-daily, fixed-dose combination tablet containing 50 mg of elbasvir, an NS5A inhibitor, and 100 mg of grazoprevir, an NS3/4A protease inhibitor, was approved for a treatment duration of 12 or 16 weeks, depending on HCV genotype and prior treatment history, as well as for patients with HCV genotype 1a infection or the presence of certain baseline NS5A polymorphisms. A 12-week, once-daily regimen is recommended for most patients, according to a press release.

According to a press release from the FDA, the product label provides recommendations regarding length of treatment with or without ribavirin specifically tailored to the characteristics of the patient and their infection.

“It is recommended that healthcare professionals screen genotype 1a-infected patients for certain viral genetic variations prior to starting treatment with Zepatier to determine dosage regimen and duration,” the release said.

The approval is supported by clinical data from the C-EDGE, C-SURFER, C-SCAPE and C-SALVAGE clinical trials, in which 1,373 patients with chronic HCV genotype 1 or 4, including treatment-naive patients, nonresponders to prior therapy, those with compensated cirrhosis or HIV-1 co-infection, were dosed with the combination regimen to determine efficacy and sustained virologic response at 12 weeks after the completion of treatment, according to the release.

“Continued innovation is needed to help address the worldwide epidemic of chronic hepatitis C virus infection,” Roger M. Perlmutter, president of Merck Research Laboratories, said in the release. “Our clinical program was designed to study a broad range of patients infected with the hepatitis C virus, including difficult-to-treat patients such as those with stage 4 or 5 chronic kidney disease. The approval of Zepatier is a testament to Merck’s unwavering commitment to improving therapy for patients with hepatitis C virus infection, and we are eager to bring this innovation to patients and physicians in the United States.”

The regimen is not intended for use in patients with moderate or severe hepatic impairment (decompensated cirrhosis) and not recommended for use with organic anion transporting polypeptides 1B1/3 (OATP1B1/3) inhibitors (e.g., atazanavir, darunavir, lopinavir, saquinavir, tipranavir, cyclosporine), strong cytochrome P450 3A (CYP3A) inducers (e.g., carbamazepine, phenytoin, rifampin, St. John’s Wort) and efavirenz, according to the release.

The FDA re-established two new designations in April 2015 for the combination regimen for patients with HCV genotype 4 and genotype 1 with end stage renal disease on hemodialysis after rescinding breakthrough designation earlier last year. The FDA originally granted breakthrough therapy designation for the drug combination in October 2013. However, in February 2015, Merck announced the FDA’s intent to rescind that designation due to the availability of other new drugs for HCV.

Disclosure: Perlmutter is employed by Merck.