Achillion Reports Promising Data on All-oral Hepatitis C Regimen with ACH-3102

Achillion Pharmaceuticals this week reported interim results from an ongoing Phase 2a study of an interferon-free regimen containing its once-daily NS5A inhibitor, ACH-3102, plus ribavirin. To date, the combination appears safe and shows potent activity against hepatitis C virus (HCV).

The recent approval of the first direct-acting antiviral agents for HCV has brought about a new treatment paradigm, but many patients and providers continue to wait for all-oral therapy that avoids interferon and its difficult side effects.

Several trials of interferon-free regimens have demonstrated good results, achieving a virological cure in large proportions of patients. The NS5A inhibitor class appears to be a particularly potent component of oral combination regimens, though these agents have not been widely studied with ribavirin alone.

Below is an edited excerpt from an Achillion press release describing the early study findings.

Achillion Reports Interim Results on ACH-3102

• Enrollment completed in pilot Phase 2a study of ACH-3102 and ribavirin for genotype 1b CC patients
• Up to 12 weeks of once daily ACH-3102 appears safe and well tolerated with no on-treatment virologic breakthrough observed to date
• Profile of ACH-3102 supportive of continued development for genotype 1b and in combination with other direct-acting antivirals for the broad treatment of HCV

New Haven, Conn. -- Jan. 7, 2013 -- Achillion Pharmaceuticals, Inc. (Nasdaq:ACHN) today announced that it has completed enrollment in a pilot Phase 2a trial evaluating ACH-3102, a second-generation pan-genotypic NS5A inhibitor, in combination with ribavirin for the treatment of patients with chronic genotype 1b (GT 1b) hepatitis C virus (HCV) infection. The initial cohort enrolled eight patients with GT 1b HCV, IL28b genotype CC, that are receiving twelve weeks of ACH-3102 once daily in combination with ribavirin.

To date, five patients have completed 4 weeks of treatment, including three patients who have completed 12 weeks of treatment. ACH-3102 has been well-tolerated by all patients with no serious adverse events, subject withdrawals, or on-treatment viral breakthrough reported to date. Treatment with ACH-3102 has resulted in rapid reduction in HCV RNA accompanied by normalization of liver enzymes.

"We are very pleased to see that the profile of ACH-3102 continues to exceed our expectations for providing a truly improved barrier to resistance. As the first-ever clinical trial to evaluate a NS5A inhibitor as a single direct-acting antiviral in combination with ribavirin, we are extremely encouraged by these initial results that demonstrate rapid suppression of the HCV GT1b virus and a well-tolerated safety profile through 12 weeks of therapy," commented Milind Deshpande, PhD, President of Research and Development and Chief Scientific Officer of Achillion. "As this data set continues to mature, we look forward to reporting initial SVR results at a medical meeting in the second quarter, and are planning to expand enrollment in the study to include non-CC GT 1b treatment-naive patients later this quarter pending regulatory discussions."

Interim Results of Phase 2a Pilot Study of ACH-3102 and ribavirin

Achillion initiated in September 2012 patient enrollment into this open-label Phase 2a pilot trial evaluating 12 weeks of once daily dosing of ACH-3102 in combination with ribavirin for the treatment of chronic HCV GT 1b infection. The study has enrolled 8 treatment-naive patients with HCV GT 1b IL28B CC genotype. Patients received 225 mg of ACH-3102 on day 1 followed by 75 mg of ACH-3102 once daily on subsequent days in combination with 1000-1200 mg dose of ribavirin. The primary objective of the trial is to determine the safety of this dosing regimen, and the sustained virologic response 12 weeks after the completion of treatment (SVR12) with secondary endpoints assessing pharmacokinetics, pharmacodynamics, and other virologic endpoints including rapid virologic response (RVR) and end of treatment response (ETR).

To date, following up to 12 weeks of treatment with ACH-3102 in combination with ribavirin, there have been no reported serious adverse events, no treatment discontinuations and no clinically significant changes in vital signs, electrocardiograms (ECGs), or laboratory evaluations with the exception of one subject with an anemia requiring a ribavirin dose reduction.

Clinical virology evaluations are ongoing including baseline and on-treatment virologic sequencing. ACH-3102 in this study demonstrates sustained antiviral activity even in subjects with multiple baseline mutations in the NS5A protein known to be highly resistant to first-generation NS5A inhibitors.

Michael D. Kishbauch, President and Chief Executive Officer of Achillion, commented, "Given the impressive safety profile and single agent activity seen to date, we feel ACH-3102 is a highly competitive compound for treating genotype 1b in combination with ribavirin and has emerged as a best-in-class agent that can be combined in multiple regimens, including sovaprevir or other DAAs, for the broad treatment of HCV."

About NS5A Inhibitors and ACH-3102

The NS5A protein is a clinically validated target that serves multiple functions at various stages of the HCV life cycle including involvement in virion production, interaction with host proteins and association with interferon-resistance. ACH-3102, Achillion's second-generation NS5A inhibitor, has demonstrated potent activity against all HCV genotypes in vitro and in preclinical studies achieved additive to synergistic activity when combined with NS3 protease inhibitors, NS5B polymerase inhibitors, interferon and ribavirin. In preclinical studies, ACH-3102 demonstrated excellent potency, in the pico-molar range, against wild type HCV RNA replication, as well as potency against resistant mutants that have been identified in clinical studies. ACH-3102 was deemed to be safe and well-tolerated in Phase 1 development and achieved mean maximal reductions in HCV RNA of 3.78 log₁₀ after a single dose. ACH-3102 has been granted fast track designation by the FDA and is currently being evaluated in Phase 2 for the treatment of GT 1b HCV.

About Achillion Pharmaceuticals

Achillion is an innovative pharmaceutical company dedicated to bringing important new treatments to patients with infectious disease. Achillion's proven discovery and development teams have advanced multiple product candidates with novel mechanisms of action. 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.

12/8/13

Source

Achillion Pharmaceuticals. Achillion Reports Promising Data on All-oral Hepatitis C Regimen with ACH-3102. Press release. January 7, 2012.