New Hepatitis C Virus Study to Assess Host-Targeted Antiviral Drug Approach

New Hepatitis C Virus Study to Assess Host-Targeted Antiviral Drug Approach

Enanta Pharmaceuticals has begun dosing chronic hepatitis C virus (HCV) patients with its investigational drug EDP-494 as part of a proof-of-concept study designed to demonstrate the medicine’s efficacy in a subset of patients with the chronic infection.

Hepatitis C is a contagious disease caused by the hepatitis C virus, and it is the most common cause of chronic liver disease. Hepatitis C is divided into six major genotypes, according to the genetic structure of the virus. It is important to identify the genotype of HCV, as it may influence the recommended treatment, its dose, and duration. Genotype 1, especially, is the most common type in the U.S. as well as the most difficult to treat.

Most therapies currently on the market act directly on the virus. But due to the high replicating rates of HCV, mutations can occur that render the virus resistant to the therapy.

Enanta developed EDP-494, a cyclophilin inhibitor that targets a protein in the human host required for the replication of HCV. Since EDP-494 acts as a host-targeted antiviral, the viral mutations that often arise from direct-acting antiviral (DAA) drugs are not expected to occur, suggesting that cyclophilin inhibitors may be the best barrier to resistance than any other class of HCV therapies.

According to data presented at April’s International Liver Congress in Barcelona, EDP-494 is a potent inhibitor of HCV replication.

In Enanta’s double-blind, randomized proof-of-concept study, Enanta will assess the safety and efficacy of two different doses of EDP-494 in patients with genotype 1 or genotype 3 HCV who have never received antiviral treatment. EDP-494’s safety and pharmacokinetics has already been addressed in multiple ascending, once-daily oral doses in healthy volunteers, and these data supported the testing of EDP-494 in HCV patients.

“As the number of patients treated with the current HCV DAA regimens on the market rapidly increases, the treatment failure population will become an important unmet medical need in patients with hepatitis C and may require new mechanisms of therapy such as cyclophilin inhibition,” said Edward J. Gane, M.D., a principal investigator of the EDP-494 study and professor of medicine at the University of Auckland, New Zealand, in a press release.

Gane is also chief hepatologist, transplant physician, and deputy director of the New Zealand Liver Transplant Unit at Auckland City Hospital.

“This host-targeted approach may prove valuable not only in the toughest to treat patients with DAA resistance, but also in the general HCV patient population, given its pangenotypic mechanism of action and high barrier to resistance,” Gane said.

When the trial is finished, Enanta plans to evaluate EDP-494 in a therapeutic combination with one or more DAAs. The company believes that a DAA-cyclophilin inhibitor combination might provide one of the highest barriers to treatment resistance in HCV patients.

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