Achillion Provides Update on Clinical
HCV Development Programs
- Drug-drug interaction study of sovaprevir and ACH-3102 completed -
- ACH-2684, second-generation protease-inhibitor, achieves comparable activity in
cirrhotic versus non-cirrhotic patients -
- Posters discussing sovaprevir, ACH-3102 and ACH-2684 to be presented at AASLD 2012 -
NEW HAVEN, Conn. (November 12, 2012) – Achillion Pharmaceuticals, Inc. (Nasdaq: ACHN) today provided an update on the sovaprevir and ACH-3102 clinical development programs and announced new Phase 1b clinical trial results on ACH-2684.
Sovaprevir and ACH-3102 Development Update
Achillion announced today the completion of a drug-drug interaction (DDI) study evaluating the combination of sovaprevir and ACH-3102. The study, conducted in 24 healthy volunteers, concluded that there was no interaction between the two investigational compounds and that both sovaprevir and ACH-3102 were safe and well-tolerated by study participants with no significant adverse events reported.
"With the completion of this DDI study, we now plan to submit to the FDA a Phase 2 protocol that will evaluate an all-oral, interferon-free regimen containing sovaprevir and ACH-3102 for 12weeks and, pending discussions with the regulatory agency, we intend to initiate this combination study with the goal of reporting rapid virologic response, or RVR, in the first half of 2013," stated Michael D. Kishbauch, President and Chief Executive Officer of Achillion.
Milind Deshpande, Ph.D., President of Research and Development and Chief Scientific Officer of Achillion commented, "We also continue to enroll and treat patients in our ongoing Phase 2 trial evaluating ACH-3102 and ribavirin for the treatment of genotype 1b CC HCV patients and, based upon emerging clinical trial results, we plan to initiate discussions with regulatory agencies to expand the enrollment to include additional genotype 1b patients and look forward to providing an update on this study later in the fourth quarter detailing RVR and safety results."
ACH-2684: Phase 1b study in Chronic HCV GT1 Cirrhotic Patients
Achillion also reported today additional proof-of-concept data from its Phase 1b clinical trial of ACH-2684, a second-generation protease inhibitor, which demonstrated that chronic genotype 1 HCV treatment-naïve patients with cirrhosis treated with 400 mg ACH-2684 once daily for three days achieved a mean maximum 3.67 log10 reduction in HCV RNA (range 3.10-4.40 log10) as compared to 0.22 log10 reduction for placebo. The antiviral activity achieved in this treatment-naïve patient population was similar to the 3.68 log10 reduction in HCV RNA innon-cirrhotic genotype 1 HCV treatment-naïve patients receiving the same dose of ACH-2684. The full dosing cohort (n=8; 6 active, 2 placebo) included one subject that received active drug who, based upon baseline viral population sequencing, was demonstrated to have nearly 100% substitution at position R155K. Presence of approximately 100% R155K mutation at baseline in subjects who have not been exposed to a protease inhibitor regimen is highly unusual and likely indicative of prior treatment that was not revealed at study enrollment. Further analysis is on-going and this patient's antiviral activity is excluded from the reductions above.
Safety data demonstrated that ACH-2684 was well tolerated in this patient population with 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.
"With the unique pharmacokinetic profile of ACH-2684, which we believe does not require active uptake of thecompound into the liver, we are very pleased to have achieved the same robust antiviral activity in patients with compensated cirrhosis," commented Dr. Deshpande. "We believe these results support the continued development of this second-generation protease inhibitor and will look to fully leverage its activity in special populations of HCV patients."
Posters Presentations by Achillion at the 63rd Annual Meeting of the American Association for the Study of Liver Diseases (AASLD):
- Poster 1171: Viral Kinetics Modeling to aid in Dose Selection Decisions for Phase-2/3 Clinical Trials, A. Agarwal, et al. Session: Clinical HCV 2. Date: Tuesday, November 13, 2012.
- Poster 1886: In vitro Studies Demonstrate a High Probability of Curing Genotype-1 Hepatitis C with Combination of a Novel NS3 Protease Inhibitor ACH-2684 and a Novel NS5A inhibitor ACH-3102, Y. Zhao, et al. Session: HCV Therapy: Pre-clinical and Early Clinical Development. Date: Tuesday, November 13, 2012.
ACH-3102, Achillion's second generation, pan-genotypic NS5A inhibitor, is a pico-molar potent compound that has been improved from first-generation NS5A inhibitors to maintain excellent potency against both wild type HCV as well as potency against resistant mutants that have been identified in clinical studies. In vitro, ACH-3102 has demonstrated potent activity against all HCV genotypes and shown additive to synergistic activity when combined with NS3 protease inhibitors, NS5B polymerase inhibitors, and ribavirin. ACH-3102 was shown to be safe and well tolerated in Phase 1 studies with potent antiviral activity achieved after a single dose. ACH-3102 is currently being evaluated in a Phase 2 trial in combination with ribavirin for 12 weeks as a treatment for chronic HCV genotype 1b.
Sovaprevir is a Phase 2 pan-genotypic HCV protease inhibitor designed and synthesized based on crystal structures of enzyme/inhibitor complex. Sovaprevir is an open chain, non-covalent, reversible inhibitor of NS3 protease. In clinical and preclinical studies, sovaprevir demonstrated high potency, unique pharmacokinetic properties and an excellent safety profile at high drug exposures. With low single-digit nanomolar potency specific to HCV, sovaprevir is equipotent against HCV genotypes 1a and 1b at IC50 of approximately 1nM. Sovaprevir achieved sustained viral response rates of approximately 80% in combination with pegylated-interferon and ribavirin for the treatment of HCV genotype 1, and will be evaluated in all-oral, interferon-free regimens, Fast Track status was granted to sovaprevir in 2012 for the treatment of chronic HCV.
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 andextensive partitioning to the liver, as well as high liver/plasma ratios inpreclinical 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 nearly 4 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 newtreatments 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.
This press release includes forward-looking statements within the meaning of thePrivate 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 expected potency, safety, tolerability, effectiveness and other characteristics of sovaprevir, ACH-3102 and ACH-2684; and Achillion's plans and timing for advancing its clinical trials, including the combination trial of sovaprevir and ACH-3102, the ongoing trial of ACH-3102 and ribavirin, and future studies of ACH-2684. 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 clinical trials of sovaprevir, ACH-2684 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 collaborationagreements with appropriate third-parties; compete successfully with other companies that are seeking to develop improved therapies for the treatment of HCV; 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 asrequired by applicable law.
Achillion Pharmaceuticals, Inc.
Tel. (203) 752-5510
Mary Kay Fenton
Achillion Pharmaceuticals, Inc.
Tel. (203) 624-7000
Christin Culotta Miller
Tel. (212) 880-5264
The Trout Group, LLC
Tel. (646) 378-2922