Gilead Seeking Approval for Hepatitis C Combo Drug in Japan and Europe

The US FDA last week approved the combo drug (trade name: Harvoni) for use in the US.

In late September, Gilead Sciences submitted an application to Japanese regulators seeking approval of a hepatitis C combination drug that includes the company’s blockbuster Sovaldi.

In submitting the application to Japan’s Pharmaceutical and Medical Devices Agency (PMDA), the California-based drug maker is seeking approval of an investigational fixed-dose combination drug to be taken once a day for the treatment of chronic genotype 1 hepatitis C virus (HCV) infection in adults, according to a company announcement. The drug combines 400 mg of sofosbuvir, a nucleotide analog polymerase inhibitor also known as Sovaldi, and 90 mg of ledipasvir, a NS5A inhibitor.

The combination drugs are investigational products in Japan and their safety and efficacy have not yet been established, noted Gilead officials. The combination drug is also under review in Europe. The US FDA last week approved the combo drug (trade name: Harvoni) for use in the US.

The announcement said approval of the drug would simplify HCV treatment in Japan among patients who have genotype 1 strain of the virus, allowing them to take just one pill a day, without the need for interferon injections and ribavirin. Traditional treatment for HCV often required interferon injections that could cause side effects so severe as to discourage some patients from seeking treatment.

More than a million people in Japan are believed to be infected with hepatitis C, a bloodborne virus that if untreated can lead to cirrhosis, liver cancer and the need for a liver transplant. Of those infected in Japan, 70% to 80% have the genotype 1 strain, according to the Gilead statement.

To support the drug application, Gilead submitted clinical trial data that included a Japanese phase 3 study that resulted in sustained virologic response (SVR) rates of 100% among patients at 12 weeks. Doctors typically consider a patient cured when SVR is achieved 12 weeks after the end of treatment.

The study was conducted in Japan among 341 patients with genotype 1 HCV, some of whom had previously been treated for the virus and others who had not, including some who had cirrhosis. In the study, 100% of the 83 treatment-naïve patients and 100% of 88 treatment-experienced patients who took 12 weeks of the ledipasvir/sofosbuvir drug, without RBV, achieved SVR12, according to Gilead. Adverse events experienced by patients were generally mild and included nasopharyngitis (28%), headache (6%) and malaise (5%).

Gilead also submitted additional data from other phase 3 studies conducted in the US, Europe, and Puerto Rico that evaluated eight, 12, or 24 weeks of the drug treatment in genotype 1 HCV patients. The company said that SVR rates of 94% to 99% were achieved in those studies among patients in ribavirin-free cohorts.

Meanwhile global prospects for the cocktail therapy brighten as Gilead received a favorable review for the ledipasvir/sofosbuvir combination from the European Medicines Agency scientific committee, the company announced. The Committee for Medicinal Products for Human USE (CHMP) “adopted a positive opinion on the company’s Marketing Authorization Application for Harvoni, the trade name for the investigational drug.

Sovaldi has already been approved by regulators in the US, European Union, Australia, and Canada. In June Gilead submitted a Japanese NDA seeking approval of sofosbuvir as a single agent in combination with ribavirin in a 12-week, oral treatment regimen, without interferon, for patients who have genotype 2 HCV infection.