|With the significant premium paid for INHX [after a nice run-up over a few months], I thought about posting to watch the other HCV players for signs of sympathy. This PR [a week later than expected], changed that to focus on only ACHN. Numbers look very good in both drugs for a Ph1 result. The market may discount the fact that they are Ph1 results... |
NEW HAVEN, Conn., Jan. 9, 2012 (GLOBE NEWSWIRE) -- Achillion Pharmaceuticals, Inc.(Nasdaq:ACHN), a leader in the discovery and development of small molecule drugs to combat the most challenging infectious diseases, today reported new clinical trial results on its portfolio of protease inhibitors including: Phase 2 interim 12-week treatment results with ACH-1625 for the treatment of genotype 1 treatment-naive hepatitis C virus (HCV), exploratory data on ACH-1625 for the treatment of HCV genotype 3, and initial proof-of-concept data for ACH-2684. Based upon these results, Achillion is planning further exploration of ACH-1625 in combination with other oral antiviral agents for the treatment of all HCV genotypes and continues to evaluate ACH-2684 in a Phase 1 clinical trial.
Michael D. Kishbauch, President and Chief Executive Officer of Achillion commented, "ACH-1625 is emerging as a fascinating and potentially superior, once-daily protease inhibitor that competes well against all other DAAs in development, regardless of their mechanism, based upon ACH-1625's safety, efficacy, genotypic coverage and emerging resistance mutation profile. Further, ACH-2684 shows preliminary promise in its ability to treat HCV, with a safety profile that looks very good, and over the next few months we will expand our clinical experience to define the dose response for its use across all HCV genotypes."
ACH-1625: Phase 2 12-Week Study Design and Interim Results
In the second segment of this ongoing Phase 2a trial, three doses of once-daily ACH-1625 (200 mg, 400 mg or 800 mg) in combination with pegylated interferon alfa-2a and ribavirin (P/R) were dosed over 12 weeks of therapy in patients with treatment-naive HCV genotype 1. Subjects were randomized and stratified by IL28B genotype, including CT and TT, which is a marker of a patient's diminished response to interferon.
Enrollment in this study of approximately 60 patients has been completed, and data on the first 35 patients enrolled were evaluated in this interim analysis. Of the patients enrolled, the majority had HCV genotype 1a (n=23/35 (66%)), with remaining patients having HCV genotype 1b (n=10) or genotype 1 (n=2). Approximately 66% of the patients were IL28B genotype CT/TT, the more difficult to treat mutation, 74% were male and approximately 14% were African American. No viral breakthroughs were observed during treatment. Preliminary results for the first 35 patients enrolled demonstrated rapid virological response (RVR) at week 4, and complete early virologic response (cEVR) and viral load reduction at week 12 as follows:
ACH-1625 Segment 2: 12-week treatment
duration assessments200 mg
N=12 Week 4 RVR: Subjects with HCV
RNA < 25 IU/mL (8/12) 67% (8/10) 1 80% (12/12) 100% Week 12 cEVR: Subjects with HCV
RNA undetectable < 25 IU/mL (11/11) 2 100% (8/8) 3 100% (12/12) 100% CC (4/4) 100% (3/3) 100% (4/4) 100% CT or TT (7/7) 100% (5/5) 100% (8/8) 100% Mean maximum HCV RNA decline
through Week 12 (log10) 4.79 5.12 4.59 (1) One patient discontinued before week 4.
Three patients discontinued treatment after week 4 but before week 12 of treatment including (2)
one patient in the 200 mg group and (3) two patients in the 400 mg dose group. "We were pleased to note that regardless of IL28B status, 100% of patients treated through 12 weeks achieved cEVR and remained undetectable at this point in the study, and the potency and unique pharmacokinetic properties of ACH-1625 appear to provide very potent antiviral coverage for all of these genotype 1 patients," commented Dr. Elizabeth A. Olek, Chief Medical Officer of Achillion. "Patients appear to have continued on-treatment viral suppression, and we therefore look forward to determining end-of-treatment response rates for the fully enrolled study and to presenting complete study results in April."
Safety results from this segment of the trial were similar to those observed in the previously reported clinical trials of ACH-1625. Over 12 weeks of co-administration of ACH-1625 plus P/R, there was one reported serious adverse event (SAE) that was deemed unrelated to ACH-1625. Most reported adverse events (AEs) in patients receiving ACH-1625 were classified as mild to moderate and were transient. The most common AEs were consistent with pegylated interferon alfa-2a and ribavirin treatment.
ACH-1625: Pilot Phase 1 Study Evaluating Antiviral Activity against HCV Genotype 3 and Clinical Virology Assessment of HCV Genotype 1
Based upon in vitro virology, as well as evolving clinical pharmacokinetic and pharmacodynamic data, a Phase 1 pilot study was conducted to evaluate the antiviral activity of ACH-1625 for the treatment of HCV genotype 3. A total of seven patients infected with HCV genotype 3 were enrolled and treated with monotherapy consisting of 400 mg ACH-1625 twice daily for 4.5 days. In this exploratory study, ACH-1625 was safe and well tolerated. The maximum HCV genotype 3 RNA viral load reduction achieved was 3.68 log10 among the six out of seven patients that achieved an antiviral response.
In addition, clinical virology analysis of patient samples obtained during the first Phase 2 28-day study segment of ACH-1625 in combination with P/R examined the resistance mutation profile following treatment. The results indicated that following 28 days of treatment with ACH-1625 the presence of highly resistant variants were not detected.
"These findings suggest that ACH-1625 maintains high concentrations in the liver, the site of infection, resulting in a unique pharmacokinetic drug profile. These positive clinical results in genotype 3, along with the strong virologic profile of ACH-1625, have led us to take a broad look at the role of ACH-1625 in our future proprietary combination regimen," commented Milind Deshpande, Ph.D., President of Research and Development and Chief Scientific Officer.
ACH-2684: Phase 1 Healthy Volunteers and HCV Genotype 1 and 3 Segments
This Phase 1 clinical study is a randomized, double-blind, placebo-controlled trial to investigate the safety, tolerability, pharmacokinetic profile and antiviral activity of ACH-2684. Healthy volunteers in the single ascending dose (SAD) segment received doses of ACH-2684 ranging from 10 mg once daily to 300 mg twice daily. The first cohorts of HCV-infected patients were enrolled and treated with ACH-2684 administered as 400 mg twice daily for 2.5 days.
ACH-2684 was well tolerated at all doses and there were no serious adverse events, no clinically significant changes in vital signs, ECGs, or laboratory evaluations. All reported adverse events were classified as mild or moderate, were transient and showed no apparent dose relationship.
Proof-of-concept was achieved with ACH-2684 in HCV genotype 1 demonstrating a maximum HCV RNA viral load reduction of 4.63 log10. Antiviral activity with ACH-2684 in HCV genotype 3 was seen with a maximum HCV RVA viral load reduction of 2.03 log10. Additional cohorts of patients with either HCV genotype 1 or HCV genotype 3 are currently being enrolled to further explore doses and viral kinetics for ACH-2684.
All-Oral Protease Inhibitor and NS5A Inhibitor Combination Will Play an Important Role
During 2012 Achillion plans to conduct a number of clinical trials to further characterize its portfolio of protease inhibitors, including ACH-1625 and ACH-2684, and its NS5A inhibitors, including ACH-2928 and ACH-3102. In addition to the ongoing Phase 1 trials with ACH-2684 and ACH-2928, Achillion plans to submit an investigational new drug (IND) application and initiate a Phase 1 clinical trial with ACH-3102 during the second quarter of 2012. During the second half of 2012, Achillion plans to initiate an all-oral interferon-free combination study which will evaluate a protease inhibitor and a NS5A inhibitor, with or without ribavirin, for the treatment of HCV.
"We believe that the protease and NS5A inhibitor combination will play an important role in the future treatment of HCV across all genotypes," commented Mr. Kishbauch. "With the robust portfolio we have discovered and developed here at Achillion, we believe we are uniquely positioned to advance a potentially best-in-class all-oral, interferon-free combination and are looking forward to initiating clinical development with this regimen later in the year."