Interferon-free Combo Treatment for Hepatitis C Approved in Japan

Japanese regulators have approved an all-oral drug regimen developed by Bristol-Meyers Squibb to treat patients with genotype 1 chronic hepatitis C, paving the way for the drug to hit the market later this year, a company spokesperson said.

The approval issued by the Japanese Ministry of Health, Labor and Welfare is for daclatsvir, an NS5A replication complex inhibitor (in vitro) and asunaprevir, a NS3/4A protease inhibitor, as a dual regimen for chronic hepatitis C (HCV) infection. The all-oral treatment‑‑without interferon injections or ribavirin‑‑is Japan’s first for patients with genotype 1 chronic HCV infection, and can also be used for patients with compensated cirrhosis, according to a release issued by Bristol-Meyers Squibb (BMS).

The company CEO Lamberto Andreotti called the authorization a milestone that “underscores the company’s commitment to delivering innovative medicines to patients with the highest unmet needs.”

The dual regimen will provide a new treatment option for Japanese patients who are not eligible for interferon (or are intolerant to it) or who failed to respond to previous treatment, the release states. Before all-oral drugs were developed, traditional HCV treatment often required interferon injections, which are known for severe side effects that may have dissuaded some patients from seeking treatment.

In Japan, BMS will market daclatasvir under the name Daklinza and asunaprevir under the name Sunvepra. The drugs are administered in combination for 24 weeks (for adults daclatasvir 60 mg once daily and asunaprevir 100 mg twice daily).

"Japan has a unique hepatitis C patient population, many of whom are older and have been unable to take, or respond to, traditional therapies, so we have a real sense of urgency to treat these patients now," Kazuaki Chayama, a lead study investigator for the drug at Hiroshima University in Japan, said in the release.

There are about 1.2 million people in Japan who have HCV and about 70% of them have the genotype 1b infection type. A significant portion of that population are over 65 with disease-related complications that reduces tolerance to interferon-based therapies, the BMS release states.

In seeking approval from Japanese regulators, BMS submitted data from a Phase 3 clinical trial of the dual regimen, which BMS states resulted in high overall sustained virologic response (SVR) 24 weeks after the end of treatment. Overall SVR was achieved by 84.7% of Japanese patients with HCV genotype 1b and by 91.9% of patients 65 or older who were either interferon-ineligible or intolerant.

Company spokesperson Carrie Fernandez said in an email that the Daklinza+Sunvepra dual regimen will likely be commercially available to patients in Japan by September. The price of the treatment is under discussion with national pricing groups but will be confirmed when the company launches its marketing campaign, she said.

Daclatasvir is at the core of the BMS pipeline and is also under regulatory review in the United States and Europe, the BMS release states. Regulatory submissions for the regimen in Taiwan and South Korea were completed in May and June 2014, respectively.

The FDA has set a target review date of November 30, 2014, for daclatasvir and asunaprevir. The US New Drug Application (NDA) also seeks approval for use of the regimen in combination with other agents for multiple genotypes, Fernandez said.

“We plan to bring Daklinza and Sunvepra to other countries in the region with similar epidemiology (ie, a high prevalence of genotype 1b),” wrote Fernandez. Results from the HALLMARK-Dual study, the Phase III multinational clinical trial investigating the Daklinza+Sunvepra Dual Regimen among genotype 1b HCV patients, demonstrated similar results to the Japan registration study and support filings in countries that have a high prevalence of genotype 1b, such as Korea and Taiwan.