Gilead Sciences, announced that the company has submitted a New Drug Application (NDA) to Japan’s Pharmaceutical and Medical Devices Agency (PMDA) for approval of an investigational once-daily fixed-dose combination of the NS5A inhibitor ledipasvir (LDV) 90 mg and the nucleotide analog polymerase inhibitor sofosbuvir (SOF) 400 mg for the treatment of chronic genotype 1 hepatitis C virus (HCV) infection in adults. The data submitted in the NDA, which include a Japanese phase 3 study showing 100 per cent SVR12 rates, support the use of LDV/SOF for 12 weeks in treatment-naïve and treatment-experienced patients with chronic genotype 1 HCV infection, including those with cirrhosis. Patients who achieve SVR12 are cured of HCV infection. If approved, LDV/SOF would simplify HCV treatment for genotype 1 patients in Japan to one daily tablet, eliminating the need for interferon and ribavirin (RBV).

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.

The NDA is based on data from a phase 3 clinical trial conducted in Japan (GS-US-337-0113) among 341 treatment-naïve and treatment-experienced genotype 1 patients. In the study, 100 per cent (n=83/83) of treatment-naïve and 100 per cent (n=88/88) of treatment-experienced patients receiving 12 weeks of LDV/SOF without RBV achieved SVR12. Adverse events observed with LDV/SOF without RBV were generally mild and included nasopharyngitis (28 per cent), headache (6 per cent) and malaise (5 per cent).

The NDA is also supported by SVR12 results from three phase 3 studies (ION-1, ION-2 and ION-3) evaluating eight, 12 or 24 weeks of LDV/SOF 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=863) achieved SVR12 rates of 94 to 99 per cent.

LDV/SOF is currently under regulatory review in the United States and European Union.

On June 27, 2014 Gilead submitted an NDA to Japan’s PMDA for SOF as a single agent in combination with RBV for the treatment of genotype 2 HCV infection. SOF as a single agent has been approved by regulatory authorities in the United States, European Union, Australia and Canada under the tradename Sovaldi®.

LDV/SOF and SOF are investigational products in Japan and their safety and efficacy have not yet been established.