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., Nov. 12, 2012 (GLOBE NEWSWIRE) -- 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 12 weeks 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
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 log reduction in HCV RNA (range 3.10-4.40 log) as
compared to 0.22 log reduction for placebo. The antiviral activity
achieved in this treatment-naïve patient population was similar to the 3.68
log reduction in HCV RNA in non-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 the compound 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
Posters Presentations by Achillion at the 63^rd 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 IC 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 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
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 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 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
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 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 collaboration agreements 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 as
required by applicable law.
CONTACT: Company Contact:
Achillion Pharmaceuticals, Inc.
Tel. (203) 752-5510
Christin Culotta Miller
Tel. (212) 880-5264
Mary Kay Fenton
Achillion Pharmaceuticals, Inc.
Tel. (203) 624-7000
The Trout Group, LLC
Tel. (646) 378-2922
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