Achillion Announces Positive Once-Daily Dosing Results With ACH-1625 to Treat Hepatitis C
May 11, 2010 (GlobeNewswire via COMTEX News Network) --
Once-Daily Dose Achieves 3.81 log10 Viral Load Reduction With Continued
Safety and Tolerability
Conference Call Begins Wednesday, May 12 at 1:15 p.m. Eastern Time
NEW HAVEN, Conn., May 11, 2010 (GLOBE NEWSWIRE) -- Achillion Pharmaceuticals, Inc. (Nasdaq:ACHN) today reported additional preliminary data from its Phase 1b clinical trial of ACH-1625, which demonstrated that both the third and fourth patient cohorts receiving treatment with ACH-1625 achieved meaningful reductions in HCV RNA after five-day monotherapy, with continued 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.
Third Dosing Cohort Results (200mg Twice Daily)
Subjects in the third cohort of HCV-infected patients received doses of 200mg twice-daily (n=9, randomized to 6 active drug, 3 placebo) for five days. Preliminary results showed that a mean maximum reduction in viral load of 3.86 log10 was achieved in the treatment group, as compared to a mean rise of 0.16 log10 in the placebo group. All subjects in the treatment group had viral load decline greater than 3.0 log10. Mean alanine aminotransferase (ALT) levels decreased over the treatment period and continued to show decline at day 12. Safety results from this dosing group were similar to those observed in previous segments 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 in patients receiving ACH-1625 were classified as mild or moderate and were transient. As seen in previous dosing cohorts, sustained viral suppression was noted with patients maintaining a mean reduction of 1.65 log10 from baseline through day 12, seven days after dosing was completed and the last day of viral load measurement in the study.
Fourth Dosing Cohort Results (600mg Once Daily)
Subjects in the fourth cohort of HCV-infected patients received doses of 600mg once-daily (n=8, randomized to 6 active drug, 2 placebo) for five days. Preliminary results showed that a mean maximum reduction in viral load of 3.81 log10 was achieved in the treatment group, as compared to a mean rise of 0.24 log10 in the placebo group. All subjects in the treatment group had viral load decline greater than 3.0 log10. Mean alanine aminotransferase (ALT) levels decreased over the treatment period and continued to show decline at day 12. Safety results from this dosing group were similar to those observed in previous segments of the trial. There was one non-drug-related serious adverse event, a bone fracture in a patient receiving placebo. There were no clinically significant changes in vital signs, electrocardiograms or laboratory evaluations. All reported adverse events in patients receiving ACH-1625 were classified as mild or moderate and were transient. Again, sustained viral suppression was noted in this dosing cohort of HCV-infected subjects, with patients maintaining a mean reduction of 2.19 log10 from baseline through day 12, seven days after dosing was completed and the last day of viral load measurement in the study.
"We continue to be pleased with the robust results from these additional cohorts of our ACH-1625 Phase 1b trial with HCV-infected patients," said Michael D. Kishbauch, Achillion's President and Chief Executive Officer. "It is impressive that at all dose levels ACH-1625 has shown meaningful viral load reduction and sustained viral suppression post treatment course. Importantly, we believe the results from these last two cohorts demonstrated that ACH-1625 was effective at a lower dosing level and in a once-daily dose, features that distinguish our drug and suggest it could offer improvements over other protease inhibitors currently in development."
He continued, "In summary, these data round out the phase 1b program for ACH-1625 very favorably. If these results are sustained through further development, we believe the combination of potency, safety/tolerability, dosing flexibility and durability of effect will position ACH-1625 as a potential best-in-class protease inhibitor, while strategically enhancing Achillion for a variety of options. We remain very encouraged by these compelling results and look forward to advancing the drug into Phase 2 studies in the coming months."
Conference Call
The Company will host a teleconference to discuss these clinical trial results on Wednesday, May 12, 2010 at 1:15 p.m. Eastern Daylight Time. Along with Achillion management, Douglas Dietrich, M.D. of Mount Sinai Medical Center, New York, will participate in the call. The call may be joined via telephone by dialing 800-776-0420 or 913-312-0968 (for international participants) at least 5 minutes prior to the start of the call and using the conference confirmation code 6476067. An audio replay will be available through midnight on May 17, 2010 by dialing (888) 203-1112 or (719) 457-0820 (international) and using the conference confirmation code 6476067.
A live audio webcast of the call will also be available on the "Investor Relations" section of the company's website, www.achillion.com. An archived audio webcast will be available on the Achillion website approximately two hours after the event and will be archived for three months.
Previous Dosing Cohort 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. 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 approximately 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 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 -- hepatitis C, resistant bacterial infections and HIV. For more information on Achillion Pharmaceuticals, please visit www.achillion.com or call 1-203-624-7000.
Forward-Looking Statements
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.