NEW HAVEN, Conn., May 21, 2012 (GLOBE NEWSWIRE) -- Achillion Pharmaceuticals, Inc. (Nasdaq:ACHN) today reported proof-of-concept data from a Phase 1b clinical trial demonstrating that patients with chronic hepatitis C (HCV) genotype 1 (GT 1) treated with ACH-2684, a second-generation protease inhibitor, achieved a mean maximum 3.73 log10 reduction in HCV RNA after three-day 400 mg monotherapy with once-daily (QD) dosing. The compound also demonstrated good safety and tolerability both in healthy volunteers and in patients with HCV.
"We believe ACH-2684, with its potent antiviral activity achieved without boosting and once-daily dosing, is one of the most intriguing protease inhibitors in clinical development for the treatment of HCV," commented Michael D. Kishbauch, President and Chief Executive Officer of Achillion. "As we continue to focus our efforts on advancing our internally developed all-oral, interferon-free HCV regimen consisting of ACH-1625, our next generation protease inhibitor, in combination with ACH-3102, a second generation pan-genotypic NS5A inhibitor, we believe that the profile of ACH-2684 provides a significant strategic and therapeutic option for potential combinations with either ACH-3102 or other direct-acting antiviral agents."
ACH-2684 Phase 1 Clinical Trial
Achillion is evaluating ACH-2684 in a Phase 1 randomized, double-blind, placebo-controlled clinical trial to investigate the safety, tolerability, pharmacokinetic profile and antiviral activity in healthy subjects and HCV-infected patients. The trial consists of three segments: Phase 1a assessment of single ascending oral doses (SAD) in healthy volunteers, Phase 1a 14-day multiple ascending doses segment (MAD) in healthy volunteers, and Phase 1b evaluation of three days of oral repeat doses in subjects with GT 1 or 3 HCV. The MAD segment of this trial will be initiated during the second quarter and full trial results are expected to be presented at a medical meeting in the fourth quarter of 2012.
During the oral repeat doses segment in subjects infected with GT 1 HCV, a total of 30 patients were enrolled including 6 patients receiving placebo and 24 patients treated with three doses of 100 mg once daily (n=8), 400 mg once daily (n=8), or 400 mg twice daily (n=8) of ACH-2684. No serious adverse events (SAE) were reported and there were no patient discontinuations during treatment. The mean maximum GT 1 HCV RNA decline during therapy for the 100 mg QD, 400 mg QD, and 400 mg BID groups were 3.36 log10, 3.73 log10, and 4.16 log10, respectively, compared to a 0.68 log10 decline for patients receiving placebo. There were no viral breakthroughs observed during ACH-2684 monotherapy. Additional assessments of GT 3 activity are currently under development.
Safety data from the SAD and HCV-infected segments of the trial demonstrated ACH-2684 was well tolerated at all doses evaluated up to and including the maximum total daily dose of 1400 mg. 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, and were transient in nature. Dosing in the 14-day MAD segment is being initiated during the second quarter with longer term safety data expected to be available in the third quarter of 2012.
ACH-2684 is a next-generation HCV protease inhibitor designed and synthesized based on crystal structures of enzyme/inhibitor complex. ACH-2684 is a macro-cyclic, non-covalent, reversible inhibitor of NS3 protease. In preclinical studies, ACH-2684 demonstrated pico-molar potency, excellent pharmacokinetic properties and safety profile at high drug exposures. ACH-2684 also exhibits rapid and extensive partitioning to the liver, as well as high liver/plasma ratios in preclinical studies. ACH-2684 has shown pico-molar potency against NS3 protease that is specific to HCV. It has preclinical activity against the 6 known genotypes of HCV and exhibits equipotent activity against HCV genotypes 1a and 1b at an IC50 of approximately 100 pico-molar. The drug candidate was discovered internally and is being advanced by Achillion.
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 including more than 5 million people in the United States, more than twice as widespread as HIV. Three-fourths of the HCV patient population is undiagnosed; it is a silent epidemic and a major global health threat. Chronic hepatitis, if left untreated, can lead to permanent liver damage that 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 HCV and resistant bacterial infections. 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 important factors that could cause actual results to differ materially from those indicated by such forward-looking statements, including statements with respect to: the potency, safety, tolerability, effectiveness and other characteristics of Achillion's ACH-2684, ACH-1625 and ACH-3102; Achillion's expectations regarding timing for the commencement, completion and reporting of results of clinical trials of drug candidates including ACH-2684, ACH-1625 and ACH-3102; and Achillion's ability to advance a potentially best-in-class all-oral, interferon-free combination of ACH-1625 and ACH-3102 and ACH-2684 in combination with ACH-3102 or other direct acting antiviral agents. Among the factors that could cause actual results to differ materially from those indicated by such forward-looking statements are risks relating to, among other things Achillion's ability to: replicate in later clinical trials positive results found in earlier stage nonclinical studies and clinical trials of ACH-2684, ACH-1625 and ACH-3102; advance the development of its drug candidates under the timelines it anticipates in current and future clinical trials; obtain necessary regulatory approvals; obtain patent protection for its drug candidates and the freedom to operate under third party intellectual property; establish commercial manufacturing arrangements; identify, enter into and maintain collaboration agreements with appropriate third-parties; compete successfully with other companies that are seeking to develop improved therapies for the treatment of HCV; manage expenses; and raise the substantial additional capital needed to achieve its business objectives. 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, 2011 and its subsequent SEC filings.
In addition, any forward-looking statement in this press release represents Achillion's views only as of the date of this press release and should not be relied upon as representing its views as of any subsequent date. Achillion disclaims any obligation to update any forward-looking statement, except as required by applicable law.
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