- Category: Experimental HCV Drugs
- Published on Friday, 19 July 2013 00:00
- Written by Achillion Pharmaceuticals
In early July the U.S. Food and Drug Administration put a clinical hold on Achillion's investigational hepatitis C virus (HCV) protease inhibitor sovaprevir (formerly ACH-1625) due to unexpected liver enzyme elevations observed in healthy volunteers taking sovaprevir with the HIV protease inhibitor atazanavir (Reyataz) in an early drug-drug interaction study.
The hold does not affect an ongoing Phase 2 trial of sovaprevir plus the HCV NS5A inhibitor ACH-3102, but may have ramifications for future trials looking at HIV/HCV coinfected individuals.
Below is an edited excerpt from a recent Achillion press release describing the FDA action.
Achillion Provides Update on Sovaprevir Development Program
Following Phase 1 drug-drug interaction study with ritonavir-boosted atazanavir showing elevated liver enzymes, sovaprevir placed on clinical hold by FDA
Ongoing enrollment and treatment of patients remains unaffected in Phase 2 -007 combination trial evaluating 12-weeks of sovaprevir and ACH-3102 for treatment-naive genotype 1 patients
New Haven, Conn. -- July 1, 2013 -- Achillion Pharmaceuticals, Inc. (Nasdaq:ACHN) today announced that the Company has received notice from the U.S. Food and Drug Administration (FDA) that a clinical hold has been placed on sovaprevir after elevations in liver enzymes associated with significantly higher than anticipated exposures to atazanavir and sovaprevir were noted in a Phase 1 healthy subject drug-drug interaction (DDI) study evaluating the effects of concomitant administration of sovaprevir with ritonavir-boosted atazanavir. The FDA has allowed continued enrollment and treatment of patients in the Phase 2 -007 clinical trial evaluating 12-weeks of sovaprevir in combination with ACH-3102 and ribavirin for patients with treatment-naive genotype 1 hepatitis C viral infection (HCV).
In a Phase 1 drug-drug interaction study, Achillion was evaluating the effects of concomitant administration of sovaprevir with ritonavir-boosted atazanavir. While conducting this study, Achillion detected unanticipated elevations in ALT liver enzymes (grade 3 or 4) in multiple subjects, although none of these met the criteria for a serious adverse event (SAE). Achillion voluntarily stopped further dosing in the DDI study and promptly notified the FDA of these findings.
Preliminary pharmacokinetic results indicate a metabolic interaction whereby plasma concentrations of both atazanavir and sovaprevir were substantially increased upon co-administration. Such ALT elevations have not been seen in the 12-week combination -007 trial, the 12-week combination -005 trial with ACH-3102 and ribavirin, or in any other drug-drug interaction studies completed with sovaprevir to date.
With the preliminary draft data on hand at the time of notification, the FDA placed sovaprevir on clinical hold. In order to resolve the clinical hold, the FDA has asked for study reports from two drug-drug interaction studies and an integrated safety analysis of on-going sovaprevir trials, each of which Achillion expects to provide to the FDA within approximately six weeks.
With respect to the ongoing -007 Phase 2 clinical trial, Achillion is treating patients in the first segment of the study and plans to release interim clinical trial results, including rapid virologic response (RVR) during the third quarter and sustained viral response (SVR) during the fourth quarter, as previously anticipated. To date, patients enrolled in the trial have received up to six weeks of combination treatment with no safety issues noted.
About Achillion Pharmaceuticals
Achillion is an innovative pharmaceutical company dedicated to bringing important new treatments to patients with infectious disease. Achillion's discovery, clinical development, and commercial teams have advanced multiple novel product candidates with proven mechanisms of action into studies and toward the market. Achillion is focused on solutions for the most challenging problems in infectious disease including HCV and resistant bacterial infections. For more information on Achillion Pharmaceuticals, please visit www.achillion.com or call 1-203-624-7000.
Achillion Pharmaceuticals. Achillion Provides Update on Sovaprevir Development Program. Press release. July 1, 2013.