NEW HAVEN, Conn., April 15, 2010 (GLOBE NEWSWIRE) -- Achillion Pharmaceuticals, Inc. (Nasdaq:ACHN) today presented data from the Company's ongoing Phase 1 clinical trial of ACH-1625 to treat hepatitis C (HCV) at the European Association for the Study of the Liver's (EASL) International Liver Congress taking place at the Reed Messe Wien Congress Center in Vienna, Austria from April 14-18, 2010.
The data were presented by Dr. Elizabeth Olek, Chief Medical Officer of Achillion, on April 15th beginning at 8 a.m. local time in a poster presentation entitled, "Virological Response, Safety, and Pharmacokinetic Profile Following Single- and Multiple-Dose Administration of ACH-0141625 Protease Inhibitor to Healthy Volunteers and HCV Genotype-1 Patients" (Abstract #2012). The data demonstrated that treatment with ACH-1625 achieved a significant reduction in HCV RNA after five-day monotherapy in patients with HCV, showed sustained viral suppression in patients with HCV for at least seven days after dosing was completed, and was generally safe and well tolerated in patients with HCV and in healthy volunteers.
ACH-1625 is an inhibitor of HCV NS3 protease that was discovered and is being developed by Achillion.
"We are delighted to present this robust data set from our Phase 1 studies of ACH-1625 at this prestigious conference. These data show significant antiviral activity and demonstrate continued suppression of viral load after drug discontinuation while maintaining a safe and tolerable safety profile," said Dr. Olek. "The sustained suppression of viral load is important as it could be a distinguishing feature and competitive advantage for our compound in comparison to other HCV therapeutics in development, given the potential implications for patient compliance and the emergence of resistance."
"On the strength of these early data, we have initiated additional dose cohorts under this protocol to explore lower doses as well as a once-daily dose. We have now fully enrolled these additional cohorts and look forward to completing them and reporting results in the coming weeks," added Dr. Olek.
In addition to the aforementioned presentation, the following poster presentations highlighting ACH-1625 will be exhibited at the EASL meeting on April 16:
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"Preclinical Antiviral Activity, Combination and Resistance of ACH-1625, A Potent HCV NS3 Protease Inhibitor" April 16 at 8 a.m. local time, Abstract #492, Presenter: Dr. Mingjun Huang, Executive Director, Virology of Achillion. Dr. Huang will present an analysis of the virology completed to date with ACH-1625 including potency, specificity and resistance profile.
- "Characterization of the Hepatoselective Distribution of ACH-1625, a Potent, Clinical Stage HCV NS3 Protease Inhibitor" April 16 at 8 a.m. local time, Abstract #172, Presenter: Dr. Kathe Stauber, Director, Preclinical Candidate Selection of Achillion. Dr. Stauber will present an analysis of the selective liver distribution of ACH-1625 by hepatic uptake transporters, as well as a summary of the pharmacokinetics and metabolic stability of ACH-1625.
"We are very pleased to have this body of scientific and clinical data on ACH-1625 presented at this year's EASL meeting, as it continues to underscore the potential of ACH-1625 as a powerful protease inhibitor for the treatment of HCV," commented Michael D. Kishbauch, Chief Executive Officer of Achillion. "We look forward to advancing the development of this promising therapeutic, which R&D Directions magazine recently ranked among its 'Top 100' investigational drugs."
Poster Presentations
Copies of the EASL poster presentations will be available beginning Friday, April 16, 2010 on Achillion's website at www.achillion.com on the "Achillion Today" page.
Proof-of-Concept Study Results
In Phase 1a safety studies with ACH-1625, subjects in the single ascending dose (SAD) segment of the study received doses ranging from 50mg to 2000mg. Subjects in the Phase 1a multiple ascending dose (MAD) segment of the study received five days of ACH-1625 up to a maximal dose of 2000mg 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, and no clinically significant changes in vital signs, electrocardiograms or laboratory evaluations. All reported adverse events were classified as mild or moderate, were transient and showed no apparent dose relationship.
In December 2009, Achillion announced proof-of-concept data from the first dosing cohort in the Phase 1b study. Subjects in this cohort of HCV-infected patients received doses of 600mg twice-daily (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, and no clinically significant changes in vital signs, electrocardiograms 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 seven 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.
In January 2010, Achillion announced results from the second dosing cohort in the Phase 1b study. HCV-infected subjects in this cohort (n=9, randomized to 6 active drug, 3 placebo) received doses of 500mg of ACH-1625 twice-daily. Preliminary results showed that a mean reduction in viral load of 4.25 log10 was achieved in the treatment group, as compared to a mean reduction of 0.29 log10 in the placebo group. Safety results from this dosing group were similar to those observed in both the Phase 1a segment of the trial and in the first cohort of HCV-infected subjects. Sustained viral suppression was also similar to the first cohort of HCV-infected subjects, with patients maintaining a mean reduction of more than 3.0 log10 from baseline through day 12, seven days after dosing was completed and the last day of viral load measurement in the study.
About ACH-1625
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.
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
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 additional dosing cohorts. 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, 2009.
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.
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