The Japanese Ministry of Health, Labour and Welfare (MHLW) has approved Gilead Sciences, Inc's Harvoni (ledipasvir 90 mg/sofosbuvir 400 mg), the first once-daily single tablet regimen for the treatment of chronic hepatitis C genotype 1 infection in adults.
Harvoni combines the NS5A inhibitor ledipasvir with the nucleotide analog polymerase inhibitor sofosbuvir, approved by the MHLW under the trade name Sovaldi in March 2015. Harvoni is indicated for the suppression of viremia in patients with genotype 1 chronic hepatitis C virus (HCV) infection with or without compensated cirrhosis, with a treatment duration of 12 weeks.
"Today's approval significantly advances the standard of care for chronic hepatitis C in Japan, as it eliminates the need for interferon and ribavirin, which can be difficult to take and to tolerate, and offers the majority of people with genotype 1 infection to be cured in as little as 12 weeks with a once-daily pill," said professor Masashi Mizokami, MD, PhD, The Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, Ichikawa, Japan.
Primarily due to HCV, Japan has one of the highest rates of liver cancer of any industrialised country. Of the more than one million people in Japan chronically infected with HCV, 70-80 per cent are infected with the genotype 1 strain of the virus.
Harvoni's approval in Japan is supported by data from 318 treatment-naïve and treatment-experienced Japanese patients with genotype 1 HCV infection randomized to ledipasvir/sofosbuvir (n=157) or ledipasvir/sofosbuvir plus ribavirin (n=161) in the phase 3 clinical trial GS-US-337-0113. Of the 318 patients enrolled in this study, 34 per cent were aged 65 years or older and 23 per cent had cirrhosis.
Among patients receiving 12 weeks of ledipasvir/sofosbuvir without ribavirin, 100 per cent (n=78/78) of treatment-naïve and 100 per cent (n=79/79) of treatment-experienced patients achieved sustained virologic response 12 weeks after completing therapy (SVR12). Adverse events observed with ledipasvir/sofosbuvir without ribavirin were generally mild and included nasopharyngitis (29 per cent), headache (7 per cent) and malaise (6 per cent).
The approval is also supported by results from three phase 3 studies (ION-1, ION-2 and ION-3) evaluating eight, 12 or 24 weeks of ledipasvir/sofosbuvir among genotype 1 HCV patients. Trial participants included patients from the United States, Europe and Puerto Rico who were treatment-naïve or who had failed previous treatment, including protease inhibitor-based regimens, and also included patients with compensated cirrhosis. Trial participants in the ribavirin-free arms (n=1,080) achieved SVR12 rates of 94 to 99 per cent.
"Harvoni is a safe, simple and well-tolerated treatment. With cure rates of up to 100 per cent and without the need for interferon or ribavirin, it offers genotype 1-infected patients a high likelihood of cure," said Norbert Bischofberger, PhD, Gilead's executive vice president, research and development, and chief scientific officer.
"We are pleased to have partnered with the medical community in Japan to demonstrate the safety and efficacy of two significant advances in the treatment of chronic hepatitis C - Harvoni for genotype 1 infection and Sovaldi for genotype 2 infection, which was approved just three months ago. We look forward to making Harvoni available in Japan as quickly as possible."