European Commission Grants Marketing Authorization for Merck’s ZEPATIER™ for the Treatment of Chronic Hepatitis C Infection

• Merck & Co

Merck has announced that the European Commission has approved ZEPATIER™ (elbasvir/grazoprevir) with or without ribavirin (RBV) for the treatment of chronic hepatitis C virus (HCV) genotype (GT) 1 or GT4 infection in adults. ZEPATIER is MSD’s once-daily, fixed-dose combination tablet containing the NS5A inhibitor elbasvir (50mg) and the NS3/4A protease inhibitor grazoprevir (100mg). This approval allows marketing of ZEPATIER tablets in the 28 countries that are members of the European Union, as well as European Economic Area members, Iceland, Liechtenstein and Norway. MSD continues to work to supply the EU market, with product launches estimated to begin between the fourth quarter of 2016 and the first quarter of 2017. Product launches are expected to continue across the EU through 2017.

“The approval of ZEPATIER in the European Union, following approvals in the United States and Canada earlier this year, is an important step in offering a new and effective treatment for millions of people infected with hepatitis C virus genotype 1 or 4,” said Dr. Roger M. Perlmutter, president, Merck Research Laboratories, a U.S.-based division of Merck & Co., Inc., Kenilworth, N.J., USA. “ZEPATIER is the most recent advance from MSD in our more than 30-year effort to combat the effects of hepatitis C virus infection, and hence, to reduce the burden of this disease around the world.”

Thousands of chronic HCV patients worldwide participated in the ZEPATIER clinical development program, which was designed to include patients with known treatment challenges, such as those with compensated cirrhosis and those for whom treatment with peginterferon plus RBV, with or without an HCV protease inhibitor, has not worked. In the trials, overall sustained virologic response (SVR) 12 weeks after the completion of therapy (SVR12, considered virologic cure based on undetectable HCV RNA levels) was achieved in 96 percent (301/312) of chronic HCV GT1b-infected patients treated with ZEPATIER for 12 weeks. In chronic HCV GT1a-infected patients, 93 percent (483/519) and 95 percent (55/58) achieved cure following treatment with ZEPATIER for 12 weeks or ZEPATIER plus RBV for 16 weeks, respectively. Additionally, 94 percent (61/65) and 100 percent (8/8) of chronic HCV GT4-infected patients achieved cure following treatment with ZEPATIER for 12 weeks or ZEPATIER plus RBV for 16 weeks, respectively.

Chronic HCV infection, caused by a blood-borne virus, is a major public health concern affecting more than 170 million people globally, 15 million of whom are living in Europe. Of the six genotypes of chronic HCV infection, GT1 is the most common in Europe accounting for approximately 66 percent of cases, and GT1b infection is the most prevalent sub-genotype in the majority of European countries. In addition, the prevalence of GT4 infection is increasing in Europe.

“Given the complexities of chronic hepatitis C, it is critical to have a variety of effective treatment options to ensure diverse types of patients have the highest possible chance to achieve cure,” said Professor Rafael Esteban, M.D., chief of the internal medicine and liver unit of the Hospital Universitario Val d’Hebron, Barcelona, Spain, and professor of medicine at the Universidad Autonoma de Barcelona. “In clinical trials, ZEPATIER achieved high cure rates among a broad range of chronic hepatitis C patients with genotype 1 or 4 infection, from patients who are treatment-naïve to many of those whose chronic HCV infection has been historically difficult-to-treat, providing an important new option in the fight against this global public health epidemic.”

A 12-week, once-daily regimen is recommended for patients with chronic HCV GT1 or GT4 infection. For certain patients, a regimen of ZEPATIER plus RBV for 16 weeks should be considered. The recommended regimens and durations for treatment with once-daily ZEPATIER in chronic HCV patients with or without compensated cirrhosis (Child-Pugh A only) are included in the chart below. No dose adjustments are required when using ZEPATIER with acid-reducing agents.

“Expanding the treatment landscape is always meaningful for the patient community as we continue to build upon the strides made in recent years to raise awareness of and treat chronic hepatitis C worldwide,” said Charles Gore, president, World Hepatitis Alliance. “Competition helps fuel dialogue and ensure people know chronic hepatitis C is treatable. With new treatment options, more patients may be able to achieve cure, and hopefully share their stories to inspire others to get treated.”

ZEPATIER Clinical Trial Program

The efficacy and safety of ZEPATIER were evaluated in eight clinical studies in approximately 2,000 patients. The development program was designed to investigate ZEPATIER across diverse chronic HCV patients, including those on opioid agonist therapy, with chronic kidney disease or with HCV/HIV-1 co-infection. The primary efficacy endpoint in all studies was SVR12. An overview of the studies is provided below. For full study details, see the Summary of Product Characteristics at http://ec.europa.eu/health/documents/community-register/2016/20160722135308/anx_135308_en.pdf.