Achillion Shows Potential for Best-in-Disease Regimen

Achillion Pharmaceuticals, Inc. recently announced positive interim results from two studies supporting a short duration, potentially best-in-disease regimen of its proprietary NS5A and nucleotide inhibitors, ACH-3102 and ACH-3422.

“We believe that achievement of 100% SVR4 in 6 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,” said Milind Deshpande, PhD, President and Chief Executive Officer of Achillion. “We look forward to initiating in 2015 short duration, pan-genotypic Phase II therapeutic trials to evaluate the doublet of ACH-3102 and ACH-3422, with the ultimate goal of improving patient care and access to treatment.”

Achillion announced 100% SVR4 results from the ongoing 6-week trial. This study is an interferon-free, ribavirin-free, Phase II open-label, randomized study to evaluate the efficacy, safety, and tolerability of 6 weeks of 50 mg of ACH-3102 and 400 mg of sofosbuvir, a marketed nucleotide polymerase inhibitor, once daily, in treatment-naïve genotype 1 HCV-infected patients. The primary objective of the study is determination of sustained viral response 12 weeks (SVR12) after completion of therapy.

Eighteen patients were enrolled, including 12 active and six observational patients. Mean baseline HCV RNA viral load was 10 million (7 log10) IU/ml, range 2 million (6.23 log10) – 97 million (7.99 log10) IU/ml, including seven patients with baseline HCV RNA viral load exceeding 6 million (6.78 log10) IU/ml. Of the 12 active patients enrolled, 10 patients were genotype 1a and two were genotype 1b.

Four weeks after the completion of therapy, 100% (n=12/12) achieved SVR4, independent of baseline viral load, gender, and IL28B status. No post-treatment viral relapse has been observed to date. SVR12 results will be reported during the first half of 2015. The combination of ACH-3102 and sofosbuvir was well-tolerated with no serious adverse events, no discontinuations due to adverse events, and no clinically significant laboratory or ECG abnormalities.

Dr. Deshpande further commented “The ACH-3102 Phase II results continue to support the best-in-class profile of our second-generation NS5A inhibitor. Despite the presence of high baseline viral loads in patients, including one patient with nearly 8 log10 HCV RNA at baseline, ACH-3102 in combination with a nucleotide demonstrated rapid suppression of viral replication. We believe the ability to achieve 100% SVR4 after only 6 weeks of therapy highlights the role ACH-3102 could play in unleashing the full potential of a NS5A-nuc combination regimen.”
Achillion also announced interim study results demonstrating that ACH-3422 achieved proof-of-concept in a Phase I trial for patients with treatment-naïve genotype 1 HCV. In the 700-mg dose group, mean maximal reduction in HCV viral RNA load of 4.8 log10 IU/ml was observed within 14 days with 3 out of 6 patients achieving undetectable HCV RNA ( < 10 IU/mL, target not detected). The pharmacodynamic characteristics of ACH-3422 provided sustained antiviral activity resulting in an additional 1.4 log10 reduction in HCV RNA between day 7 and day 14 of dosing.

“The safety profile, potent antiviral activity, and high barrier to resistance observed with ACH-3422 in this Phase I 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 II 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.”

This adaptive design Phase I trial is a randomized, double-blind, placebo-controlled trial investigating the safety, tolerability, pharmacokinetics, and antiviral activity of ACH-3422. The trial has evaluated escalating doses ranging from 50 mg to 700 mg of ACH-3422 in healthy volunteers in single ascending dose cohorts followed by 14-day multiple ascending dose cohorts. All doses were well-tolerated with no significant adverse events, ECG, or laboratory abnormalities noted. Cohorts of treatment-naïve genotype 1 HCV-infected patients were enrolled and received once-daily treatment with ACH-3422. Patients in the 50-mg, 150-mg, and 300-mg cohorts received 7 days of treatment; patients in the 500-mg and 700-mg cohorts were treated for 14 days. All doses of ACH-3422 were well-tolerated with no treatment-related SAEs, no discontinuations due to adverse events, and no clinically significant laboratory or ECG abnormalities.

Achillion is seeking to apply its expertise in biology and structure-guided design and a deep understanding of patient and clinician needs to develop innovative treatment solutions aimed at improving patients’ lives. The company’s scientific excellence, integrated capabilities and experienced team position it to successfully achieve its goal of advancing new products along the entire continuum from the bench to the patient. Achillion’s pipeline is currently focused on small molecule therapeutics for infectious disease and complement-related diseases. www.achillion.com.