Date: 2014-06-15
Type of information: Results
phase: 3
Announcement: results
Company: Gilead (USA)
Product: ledipasvir/sofosbuvir fixed-dose combination
Action
mechanism: direct-acting antiviral agent/nucleotide analog. Sofosbuvir is an oral nucleotide analog inhibitor of the HCV NS5B polymerase enzyme, which plays an essential role in HCV replication. This direct-acting agent interferes directly with the HCV life cycle by suppressing viral replication.
Disease: genotype 1 hepatitis C
Therapeutic area: Infectious diseases
Country: Japan
Trial
details: This phase 3b study evaluates the antiviral efficacy of sofosbuvir (SOF)/ledipasvir (LDV) fixed-dose combination (FDC) with or without ribavirin (RBV) in treatment-naive or treatment-experienced Japanese participants with chronic genotype 1 HCV infection at approximately 20 sites in Japan. Participants receive 12 weeks of treatment and continue assessments during a 24-week follow-up. (NCT01975675)
Latest
news: * On June 15, 2014, Gilead Sciences 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% (n=83/83) of treatment-naïve and 100 % (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 % (n=80/83) of treatment-naïve and 100 % of treatment-experienced patients (n=87/87) achieved SVR12. Across all arms of the study, patients with cirrhosis achieved a 99 % (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. 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. The intent-to-treat SVR12 rates in the study are summarized in the table below: Population Treatment Duration SVR12 Rates Genotype 1 LDV/SOF 12 weeks 100% (83/83) treatment-naive LDV/SOF + RBV 12 weeks 96% (80/83) Genotype 1 LDV/SOF 12 weeks 100% (88/88) treatment-experienced LDV/SOF + RBV 12 weeks 100% (87/87) Overall, 338/341 patients (99 percent) 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 percent of patients taking LDV/SOF plus RBV compared to 2 percent of patients receiving LDV/SOF alone. Adverse events observed with LDV/SOF without RBV were generally mild and included nasopharyngitis (28 percent), headache (6 percent) and malaise (5 percent). 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.
