[Well, safety continues to look good. However, given the Feuerstein EASL article posted in #msg-61450753 which cited 80% RVR as kind of a minimum goal regarding efficacy and 90% to show superiority, I wonder if the market will be disappointed with the 75-81% RVR rate. However, perhaps that lower number is to be expected given that a large percentage of these patients were of the HCV genotype CT/TT, who apparently have a diminished response to interferon.]
Achillion Announces Positive RVR Results With ACH-1625 to Treat Chronic Hepatitis C Once-Daily Dose Achieves 75 - 81% RVR in a Well Tolerated Combination Regimen
NEW HAVEN, Conn., March 30, 2011 (GLOBE NEWSWIRE) -- Achillion Pharmaceuticals, Inc. (Nasdaq:ACHN - News) today announced top-line results from its on-going Phase 2a clinical trial of ACH-1625 dosed once daily (QD) in combination with Pegasys(R) (peginterferon alfa-2a) and Copegus(R) (ribavirin), a current standard of care (SOC) in patients with chronic hepatitis C (HCV) infection. The analysis demonstrated that 75-81% of patients receiving ACH-1625 achieved rapid virologic response (RVR) with a promising safety and tolerability profile. ACH-1625 is an inhibitor of HCV NS3 protease that was discovered by and is being developed by Achillion.
Study Design
In this first of a two segment Phase 2a trial, a total of 64 patients were enrolled and randomized across three doses of ACH-1625 given once daily (200mg, 400mg or 800mg) or placebo with peginterferon alfa-2a and ribavirin, and were dosed for 4 weeks of therapy. Patients then continue on SOC for up to an additional 44 weeks. Subjects were randomized and stratified by HCV genotype and IL28B genotype.
Top-line Results
The majority of the 64 patients enrolled were HCV genotype 1a (73%), with a smaller percentage of HCV genotype 1b patients (25%). A total of 75% of the patients enrolled were genotype CT/TT, a marker of the patient's diminished response to interferon, and 25% were genotype CC. All patients receiving 4 weeks of treatment with ACH-1625 demonstrated continuous and substantial declines in HCV RNA with no viral breakthrough during therapy at any of the doses. Preliminary results for the 64 patients enrolled demonstrate RVR percent and viral load reduction as follows:
[See Link for Table]
Safety results from a planned safety analysis included 56 patients from this segment of the trial and indicated that adverse events (AEs) were similar to those observed in the previously reported Phase 1a and 1b trials of ACH-1625. Over 4 weeks of co-administration of ACH-1625 with SOC, there were no discontinuations due to adverse events and there were no serious adverse events (SAEs) reported. Most reported AEs in patients receiving ACH-1625 were classified as mild to moderate and were transient. The most common AEs were consistent with peginterferon alfa-2a and ribavirin.
"These data reflect a positive outcome with high RVR, irrespective of IL28B status, which places ACH-1625 among the most potent protease inhibitors in development," commented Elizabeth A. Olek, M.D., Vice President and Chief Medical Officer of Achillion. "We look forward to selecting two of these doses and beginning the second segment of the trial, dosing ACH-1625 with SOC over 12 weeks, and anticipate reporting cEVR data by the end of this year."
"We are quite pleased with the continued robust efficacy results and good safety profile with once-daily doses of ACH-1625," said Michael D. Kishbauch, Achillion's President and Chief Executive Officer. "ACH-1625 continues to demonstrate best-in-class features, including once-daily dosing, robust antiviral activity, coupled with safety and tolerability for patients. These attributes distinguish our drug and suggest it could offer improvements over other next-generation protease inhibitors that will reach the market mid-decade."
The preliminary safety profile of ACH-1625 continues to support future plans to combine this protease inhibitor with other directly acting antiviral agents. Achillion expects to initiate during 2012 a clinical trial evaluating ACH-1625 in combination with ACH-2928, an internally discovered and developed NS5A inhibitor.
About ACH-1625
ACH-1625 is a HCV protease inhibitor designed and synthesized based on crystal structures of enzyme/inhibitor complex. ACH-1625 is an open chain, non-covalent, reversible inhibitor of NS3 protease. In preclinical studies, ACH-1625 demonstrated high potency, unique pharmacokinetic properties and an excellent safety profile at high drug exposures. ACH-1625 has rapid and extensive partitioning to the liver, as well as high liver/plasma ratios. ACH-1625 has shown low single-digit nanomolar potency that is specific to HCV. It is equipotent against HCV genotypes 1a and 1b at IC50 of approximately 1nM.
In Phase 1a clinical studies, subjects receiving both single and multiple ascending doses ranging from 50 mg to 2000 mg per day for periods up to 5 days demonstrated that ACH-1625 was well tolerated at all doses and there were no SAEs, and no clinically significant changes in vital signs, electrocardiograms or laboratory evaluations. In Phase 1b clinical studies, HCV-infected patients receiving doses ranging from 200 to 600 mg twice daily, and 400 to 600 mg once daily, showed mean maximal reductions in viral load ranging from of 3.63 log10 to 4.25 log10. Furthermore, all patients had viral loads that remained suppressed for at least 7 days after dosing was completed, maintaining a mean reduction of at least 1log10 from baseline through day 12, the last day of viral load measurement in the study.
About HCV
The hepatitis C virus is the most common cause of viral hepatitis, which is an inflammation of the liver. It is currently estimated that more than 170 million people are infected with HCV worldwide and The American Association of Liver Disease estimates that up to 80% of individuals become chronically infected following exposure to the virus. If left untreated, chronic hepatitis can lead to permanent liver damage, which can result in the development of liver cancer, liver failure or death. Few therapeutic options currently exist for the treatment of HCV infection. The current standard of care is limited by its specificity for certain types of HCV, significant side-effect profile, and injectable route of administration.
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 hepatitis C and resistant bacterial infections. For more information on Achillion Pharmaceuticals, please visit www.achillion.com or call 1-203-624-7000.
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