Achillion Announces Positive Preliminary Phase 1b Proof of Concept Data With ACH-1625 to Treat Hepatitis C
Achieves 3.94 log10 Reduction in HCV RNA With Continued Safety and Tolerability
NEW HAVEN, Conn., Dec 15, 2009 (GlobeNewswire via COMTEX News Network) -- Achillion Pharmaceuticals, Inc. (Nasdaq:ACHN) today reported proof of concept data from the preliminary results of its phase 1b clinical trial of ACH-1625, demonstrating that treatment with ACH-1625 achieved a mean 3.94 log10 reduction in HCV RNA after five-day monotherapy, with continued good safety and tolerability in patients with hepatitis C (HCV). ACH-1625 is an inhibitor of HCV NS3 protease that was discovered and is being developed by Achillion.
The Phase 1 Program
In June 2009, Achillion initiated dosing in a randomized, double-blind, placebo-controlled phase 1a/1b clinical trial to investigate the safety, tolerability, pharmacokinetic profile and antiviral activity of ACH-1625 after single and multiple ascending oral doses in healthy volunteers and oral repeat doses for 5 days in subjects with hepatitis C infection. The trial is taking place in Europe and will enroll at least 54 subjects, including both healthy volunteers and HCV-infected patients.
In September 2009, Achillion announced positive results from the phase 1a segment of the study. Subjects in the phase 1a single ascending dose (SAD) segment of the study received single doses of ACH-1625 ranging from 50 mg to 2000 mg. Subjects in the phase 1a multiple ascending dose (MAD) segment of the study received 5 days of ACH-1625 up to a maximal dose of 2000 mg per day.
Preliminary data from the SAD and MAD trial segments demonstrated ACH-1625 was well tolerated at all doses and there were no serious adverse events, no clinically significant changes in vital signs, electrocardiograms (ECGs), or laboratory evaluations. All reported adverse events were classified as mild or moderate, were transient and showed no apparent dose relationship.
Today, Achillion announced proof of concept data from the preliminary results of the phase 1b segment of the study. Subjects in this first dosing cohort of HCV-infected patients received doses of 600 mg BID (n=9, randomized to 6 active drug, 3 placebo). Preliminary results showed that a mean reduction in viral load of 3.94 log10 was achieved in the treatment group, as compared to a mean reduction of 0.22 log10 in the placebo group. All subjects in the treatment group had viral load decline between 3.0 and 4.5 log10, and two subjects reached undetectable levels of HCV RNA. Safety results from this dosing group were similar to those observed in the phase 1a segment of the trial. 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.
Furthermore, all patients had viral loads that remained suppressed for at least 7 days after dosing was completed, maintaining a mean reduction of more than 2.0 log10 from baseline through day 12, the last day of viral load measurement in the study.
Preliminary analysis of viral dynamics of ACH-1625 demonstrates a very rapid reduction in HCV RNA levels after the first dose. ACH-1625 displays high efficiency for inhibition of viral production, with mean efficiency of 0.9994 out of maximal efficiency of 1.0000.
"In addition to the dramatic reduction in viral load after 5 days of monotherapy, ACH-1625 demonstrates slow viral rebound, which is an important differentiating characteristic, as this continued suppression of viral load after discontinuation of the drug may translate into a more durable antiviral response," noted Dr. Elizabeth Olek, Chief Medical Officer at Achillion. "These positive proof-of-concept results corroborate our findings from pre-clinical studies with ACH-1625, which demonstrated high potency, unique pharmacokinetic properties, and an excellent safety profile."
Michael Kishbauch, President and Chief Executive Officer of Achillion, commented on the positive results, "These compelling interim results are very encouraging as we continue to advance the clinical development of this compound for the treatment of HCV. Not only are the results especially robust, but they give us proof-of-concept ahead of schedule. This is a credit to our top-notch research and development team, which deserves recognition for its scientific excellence and tireless efforts."
"We look forward to sharing additional data from the next cohort of the phase 1b study in early January 2010, when we plan to host an investor conference call to review both segments of the phase 1 trial, in addition to updates on other Achillion progress. In addition, we expect to present the full data set from the phase 1a and phase 1b study at the upcoming EASL (European Association for the Study of Liver Disease) meeting in April 2010 in Vienna," concluded Mr. Kishbauch.
ACH-1625 is an 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. With its rapid and extensive partitioning to the liver, as well as high liver/plasma ratios demonstrated in preclinical studies, Achillion believes that ACH-1625 has the potential for once daily dosing. 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 ~1nM.
The hepatitis C virus (HCV) 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.
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 -- hepatitis C, resistant bacterial infections and HIV. For more information on Achillion Pharmaceuticals, please visit www.achillion.com or call 1-203-624-7000.
This press release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 that are subject to risks, uncertainties and other factors, including statements with respect to the potency, safety and other characteristics of ACH-1625, which may not be duplicated in future cohorts at different doses or in future clinical studies of longer duration; Achillion's expectations regarding timing and duration of other clinical trials, including cohort 6. Among the factors that could cause actual results to differ materially from those indicated by such forward-looking statements are: uncertainties relating to results of clinical trials, unexpected regulatory actions or delays, and Achillion's ability to obtain additional funding required to conduct its research, development and commercialization activities. These and other risks are described in the reports filed by Achillion with the U.S. Securities and Exchange Commission, including its Annual Report on Form 10-K for the fiscal year ended December 31, 2008.
All forward-looking statements reflect Achillion's expectations only as of the date of this release and should not be relied upon as reflecting Achillion's views, expectations or beliefs at any date subsequent to the date of this release. Achillion anticipates that subsequent events and developments may cause these views, expectations and beliefs to change. However, while Achillion may elect to update these forward-looking statements at some point in the future, it specifically disclaims any obligation to do so.