Ribavirin-Free Regimen (ACH-3102/Sofosbuvir) Achieves 100% Response Rate in HCV Patients
Interim data reported from mid-stage trial
Positive interim results have been reported from an ongoing phase II proxy study evaluating ACH-3102 (Achillion Pharmaceuticals), a second-generation nonstructural protein 5A (NS5A) inhibitor, in combination with sofosbuvir (Sovaldi, Gilead) and without ribavirin, for 8 weeks of therapy in patients with treatment-naïve genotype-1 chronic hepatitis C virus (HCV) infection.
All of the 12 treated patients remained HCV RNA undetectable 4 weeks after completing therapy (SVR4). Based on these results, 12 additional patients will begin 6 weeks of treatment with once-daily ACH-3102 and sofosbuvir.
The open-label, randomized, partial-crossover study is being conducted to evaluate the efficacy, safety, and tolerability of 8 weeks or 6 weeks of treatment with ACH-3102 and sofosbuvir — a nucleotide polymerase inhibitor — without ribavirin in treatment-naïve genotype-1 HCV-infected patients. The study’s primary objective is to determine the sustained viral response 12 weeks after the completion of therapy.
Eighteen patients were enrolled, including six observational patients. Twelve patients completed 8 weeks of treatment consisting of 50 mg of ACH-3102 and 400 mg of sofosbuvir administered once daily, whereas the observational patients received no drug during this phase of the trial. Ten of the 12 patients receiving 8 weeks of treatment had genotype-1a HCV with median HCV RNA at baseline of 7.22 log10 (range: 5.5–7.8 log10).
No on-treatment viral breakthrough or post-treatment viral relapse has been observed to date. ACH-3102 and sofosbuvir were well-tolerated, and no significant adverse events, electrocardiogram findings, or laboratory results were reported during treatment.
The six observational patients plus six additional patients will receive 6 weeks of treatment consisting of 50 mg of ACH-3102 and 400 mg of sofosbuvir administered once daily. SVR4 results from the crossover cohort are expected to be available by the end of 2014.
HCV is the most common cause of viral hepatitis. It is estimated that more than 150 million people are infected with HCV worldwide, including more than 5 million people in the U.S. Three-fourths of the HCV patient population is undiagnosed. If left untreated, chronic hepatitis can lead to permanent liver damage, which can result in the development of liver cancer, liver failure, or death.
Source: Achillion Pharmaceuticals; August 15, 2014.