Achillion has high hopes for HCV regimen

Phase 2 trial sees 100 percent SVR4 response from patients in NS5A-Nuc regimen of ACH-3102 and sofosbuvir

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NEW HAVEN, Conn.—As Achillion Pharmaceuticals Inc. advances two potential HCV therapies through the clinic, the company has seen results that could make for a best-in-disease regimen.
The Phase 2 “Proxy Study” consisted of a six-week treatment regimen of ACH-3102, second-generation NS5A inhibitor, and sofosbuvir for treatment-naive genotype 1 HCV. This interferon-free, ribavirin-free study is meant to assess the efficacy, safety and tolerability of six weeks of 50 mg of ACH-3102 and 400 mg of sofosbuvir, a marketed nucleotide polymerase inhibitor, once daily. The primary objective is determination of sustained viral response 12 weeks (SVR12) after completion of therapy. The study consists of 18 patients, 12 active and six observational patients.
Four weeks after therapy was completed, 100 percent (12 of 12 active patients) achieved SVR4, independent of baseline viral load, gender and IL28B status, with no post-treatment viral relapse observed to date. In addition, the combination therapy was well-tolerated, with no serious adverse events, no discontinuations due to adverse events and no clinically significant laboratory or ECG abnormalities.

"We believe that achievement of 100 percent SVR4 in six weeks in the ACH-3102 proxy study, combined with the high potency and safety demonstrated by ACH-3422, highlights the ability of our exceptional, fully owned portfolio to excel in the HCV market," Dr. Milind Deshpande, president and CEO of Achillion, commented in a statement. "We look forward to initiating in 2015 short duration, pan-genotypic Phase 2 therapeutic trials to evaluate the doublet of ACH-3102 and ACH-3422, with the ultimate goal of improving patient care and access to treatment."
Interim study results were also released for ACH-3422, demonstrating that the compound achieved proof of concept in a Phase 1 trial of patients with treatment-naive genotype 1 HCV. The Phase 1 trial is a randomized, double-blind, placebo-controlled trial evaluating the safety, tolerability, pharmacokinetics and antiviral activity of ACH-3422. The trial features escalating doses of ACH-3422 ranging from 50 mg to 700 mg in healthy volunteers in single ascending dose cohorts, followed by 14-day multiple ascending dose cohorts. All doses proved to be well-tolerated, with no significant adverse events. The 700 mg dose group saw mean maximal reduction in HCV viral RNA load of 4.8 log10 IU/ml within 14 days, with three out of six patients achieving undetectable HCV RNA. ACH-3422's pharmacodynamic characteristics proved capable of providing sustained antiviral activity, which resulted in an additional 1.4 log10 reduction in HCV RNA between day seven and day 14 of dosing.

"The safety profile, potent antiviral activity, and high barrier to resistance observed with ACH-3422 in this Phase 1 trial exhibit the important characteristics a nucleotide inhibitor provides in HCV treatment regimens," commented Dr. David Apelian, Executive Vice President of Clinical Development and Chief Medical Officer at Achillion. "The data, combined with the Phase 2 proxy study results, lead us to believe that the doublet regimen of ACH-3102 and ACH-3422 can be a highly competitive, regimen to cure HCV. Furthermore, the ability to explore a triplet regimen with sovaprevir, our protease inhibitor, may allow for shorter treatment durations especially in harder-to-treat patient populations."
Currently, it is estimated that some 3.2 million people in the United States have chronic hepatitis C infection, according to the U.S. Centers for Disease Control. The World Health Organization estimates that the number of individuals infected globally is somewhere in the range of 130 million to 150 million, adding that an estimated 350,000 to 500,000 people die annually from hepatitis C-related liver diseases.

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