ICAAC 2015: New Hepatitis C NS5A Inhibitor Looks Promising in Early Studies

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A new hepatitis C virus (HCV) NS5A inhibitor being developed by Enanta -- EDP-239 -- was well-tolerated and demonstrated promising antiviral activity against genotype 1 HCV in a single-dose monotherapy study presented at the 55th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) last week in San Diego.

The advent of direct-acting antiviral agents that can be used in interferon-free regimens has brought about a revolution in the treatment of chronic hepatitis C. While current approved options -- including Gilead Sciences' sofosbuvir (Sovaldi) and sofosbuvir/ledipasvir (Harvoni), AbbVie's paritaprevir/ombitasvir-based combos (Viekira Pak and Technivie), and Bristol-Myers Squibb's daclatasvir (Daklinza) -- are highly effective and well-tolerated, their high cost leaves an opening for less expensive therapies.

EDP-239 is now being developed by Enanta, after Novartis withdrew from a collaboration. Enanta was also a partner in the development of paritaprevir.

Eric Lawitz from the Texas Liver Institute in San Antonio and colleagues conducted a randomized, double-blind, placebo-controlled clinical trial to evaluate the safety and efficacy of EDP-239.

The study included 28 previously untreated chronic hepatitis C patients without liver cirrhosis, equally distributed between genotype 1a and 1b. Participants were allocated to receive EDP-239 at single oral doses of 10, 30, 100, or 200 mg, or else placebo.

Results

  • EDP-239 led to a rapid decline of HCV RNA levels starting about 2 hours after dosing, with the maximum effect seen at day 2 to 4.
  • Maximum viral load reductions ranged from approximately -2 to more than -4 log. The 100 mg dose produced the most potent antiviral activity, followed by the 200 mg dose.
  • The drug was more active against HCV genotype 1b compared to harder-to-treat 1a.
  • EDP-239 was generally safe and well-tolerated.
  • 5 EDP-239 recipients (21%) and 1 placebo recipient (25%) reported self-limited adverse events, but there were no serious adverse events.
  • The mean terminal half-life of EDP-239 in the body was approximately 24 hours.

Two related posters by Lijuan Jiang of Enanta and colleagues reported promising data on the pharmacokinetics, safety, and tolerability of EDP-239 in both healthy HCV-negative volunteers and people with hepatitis C, finding that therapeutic drug levels could be reached with achievable doses, and no safety or tolerability issues were identified.

Based on these results, the researchers concluded that EDP-239 is a potent NS5A inhibitor for treating HCV infection and the findings support the development of EDP-239 as part of combination regimens to treat HCV infection.

9/25/15

References

E Lawitz, F Poordad, J Rondon, T Box, K Tack, et al. EDP-239, a Novel HCV NS5A Inhibitor, Demonstrates Potent Antiviral Activity after a Single Dose Treatment of Genotype 1 HCV Patients. 55th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC). San Diego, September 17-21, 2015.

L Jiang, X Jiang, K Dole, et al. Pharmacokinetics, Safety, and Tolerability of EDP239, a Novel Hepatitis C NS5A Inhibitor, in Healthy Volunteers. 55th Interscience Conference on Antimicrobial Agents and Chemmotherapy (ICAAC). San Diego, September 17-21, 2015. Abstract V-446.

L Jiang, K Dole, E Lawitz, et al. Pharmacokinetics, Safety and Tolerability of EDP-239, a Novel Hepatitis C (HCV) NS5A Inhibitor, in Patients with HCV Infection. 55th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC). San Diego, September 17-21, 2015. Abstract V-448.