Gilead Sciences, Inc., a biopharmaceutical company, announced topline results from a phase 3 clinical trial (GS-US-337-0113) in Japan evaluating the investigational once-daily fixed-dose combination of the NS5A inhibitor ledipasvir (LDV) 90 mg and the nucleotide analog polymerase inhibitor sofosbuvir (SOF) 400 mg, with and without ribavirin (RBV), for the treatment of genotype 1 chronic hepatitis C virus (HCV) infection.

Among patients receiving 12 weeks of LDV/SOF without RBV, 100 per cent (n=83/83) of treatment-naïve and 100 per cent (n=88/88) of treatment-experienced patients achieved a sustained virologic response 12 weeks after completing therapy (SVR12). Among patients receiving LDV/SOF plus RBV, 96 per cent (n=80/83) of treatment-naïve and 100 per cent of treatment-experienced patients (n=87/87) achieved SVR12. Across all arms of the study, patients with cirrhosis achieved a 99 per cent (n=75/76) SVR12. The study met its primary endpoint of superiority compared to a predefined historical SVR12 rate. Patients who achieve SVR12 are considered cured of HCV infection.

Genotype 1 is the most common strain of HCV in Japan, accounting for approximately 70 per cent of the more than one million people chronically infected with the disease. The majority of these infections are due to HCV genotype 1b. Current treatment options for genotype 1 HCV infection involve up to 48 weeks of therapy with pegylated interferon injections, RBV tablets and other oral medicines, which may not be suitable for certain patients.

“The cure rates observed with LDV/SOF in this study are impressive because they were achieved without the need for interferon or ribavirin, both of which involve more complex dosing requirements and may be associated with significant side effects,” said Norbert Bischofberger, PhD, Gilead’s executive vice president of research and development and chief scientific officer. “These results suggest that a once-daily LDV/SOF tablet has the potential to be an efficacious and well-tolerated regimen for many HCV patients in Japan.”

In the study, 341 patients with genotype 1 HCV infection were randomized (1:1) to receive 12 weeks of all-oral therapy with LDV/SOF, with or without RBV. Of these, 166 patients were treatment-naïve, 175 were treatment-experienced and 76 had compensated cirrhosis.

Overall, 338/341 patients (99 per cent) in Study GS-US-337-0113 achieved SVR12. Of the three patients who failed to achieve SVR12, one patient relapsed after discontinuation of therapy, one patient discontinued therapy after one week of treatment due to rash and one patient died during the study.

Fewer adverse events were observed in the RBV-free arms compared to the RBV-containing arms in the study, most notably with regard to anemia, which was observed in 14 per cent of patients taking LDV/SOF plus RBV compared to 2 per cent of patients receiving LDV/SOF alone. 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). Among those taking LDV/SOF plus RBV, in addition to anemia, the most common adverse events were nasopharyngitis (22 percent), pruritus (8 percent), rash (8 percent), headache (8 percent), stomatitis (6 percent), nausea (5 percent) and malaise (5 percent). No patients taking LDV/SOF and two patients taking LDV/SOF plus RBV discontinued treatment due to treatment-emergent adverse events. Full study results will be presented at a future scientific meeting.

Based on these data, Gilead plans to submit a New Drug Application for the LDV/SOF fixed-dose combination with the Japanese Pharmaceutical and Medical Devices Agency (PMDA) by the end of 2014. The product is currently under regulatory review in the United States and European Union.

On April 2, 2014, Gilead announced topline results from another phase 3 study in Japan evaluating SOF as a single agent in combination with RBV for the treatment of genotype 2 HCV infection. The company plans to file for approval of SOF with the PMDA by mid-2014. SOF as a single agent has been approved by regulatory authorities in the United States, European Union 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.

Gilead Sciences is a biopharmaceutical company that discovers, develops and commercializes innovative therapeutics in areas of unmet medical need. The company’s mission is to advance the care of patients suffering from life-threatening diseases worldwide.