Gilead Files Fixed-Dose Hepatitis C Combo NDA for Japanese Market

Gilead Files Fixed-Dose Hepatitis C Combo NDA for Japanese Market

shutterstock_216751318Gilead Sciences, Inc. recently submitted a New Drug Application (NDA) to the Pharmaceutical and Medical Devices Agency (PMDA) in Japan for approval of an experimental combination therapy of the NS5A inhibitor ledipasvir (LDV), given once a day with a fixed-dose of 90 mg, and sofosbuvir (SOF) (400 mg), the nucleotide analog polymerase inhibitor, a drug with a potent antiviral activity against all identified HCV genotypes, for the treatment of chronic genotype 1 hepatitis C virus (HCV) infection in adults.

Hepatitis C (HCV) is a disease of the liver caused by the hepatitis C virus, which is a blood-borne virus. The infection can induce liver damage, and patients that are chronically infected will probably develop liver pathologies, such as cirrhosis (destruction of normal liver tissue) and cancer. Japan is has the highest rates of liver cancer along all industrialized nations. More than one million people in Japan have chronic Hepatitis C virus (HCV), among which 70-80% of the patients have the genotype 1 strain of the virus.

The NDA is supported by data from a Phase 3 clinical trial conducted in Japan (GS-US-337-0113). In this study, it was observed that 100% of naïve (n=88) and experienced genotype 1 patients (n=88), including those with cirrhosis, treated with the combination LDV/SOF therapy without ribavirin (RBV), a drug that inhibits the virus of hepatitis C from replicating inside the cells, for 12 weeks, achieved undetectable HCV viral load 12 weeks (SVR12) after completion of therapy. Importantly, these patients were cured of HCV infection. The adverse events observed during this study were normally mild and included nasopharyngitis (28%), headache (6%) and malaise (5%). In the case of approval for the combination LDV/SOF therapy in patients with genotype 1 HCV this will decrease the treatment to one daily tablet, eliminating the need for interferon and RBV.

The NDA also includes the results from three Phase 3 studies (ION-1, ION-2 and ION-3) that evaluated LDV/SOF therapy for 8, 12 or 24 weeks in genotype 1 HCV patients. The trial included patients from the United States, Europe and Puerto Rico who were treatment-naïve or who had failed previous treatment, including protease inhibitor-based therapies, and patients with compensated cirrhosis, i.e. patients with still functional diseased liver. Trial participants in the ribavirin-free arms (n=863) achieved SVR12 rates of 94 to 99%.

The combination LDV and SOF therapy is currently under regulatory review in the United States and European Union. SOF, as a single therapy, was approved by regulatory authorities in the United States, European Union, Australia and Canada under the trademark Sovaldi.

In Japan, the LDV/SOF therapy and SOF are investigational products and their safety and efficacy have not yet been established.

Finally, in late June, Gilead submitted a New Drug Application (NDA) to the Pharmaceutical and Medical Devices Agency (PMDA) in Japan, for SOF as a single agent in combination with RBV for the treatment of genotype 2 HCV infection.




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