- Results indicate up to 100% inhibition of alternative-pathway (AP) activity in hemolysis and Wieslab
assays after oral dosing of ACH-4471 -
- Results support initiation of phase 1 multiple-ascending trial during the second quarter and phase 2
studies for paroxysmal nocturnal hemoglobinuria (PNH) and C3 glomerulopathy (C3G) by year-end 2016 -
NEW HAVEN, Conn., June 10, 2016 (GLOBE NEWSWIRE) -- Achillion Pharmaceuticals, Inc. (Nasdaq:ACHN)
today presented interim results from a phase 1 study with its novel small molecule factor D inhibitor, ACH-4471, at the
21st Congress of the European Hematology Association in Copenhagen, Denmark.
The e-poster entitled, "An Orally Administered Small Molecule Factor D Inhibitor (ACH-4471) For Treatment
of PNH, C3G and Complement – Mediated Diseases: Interim Phase 1 Results In Healthy Volunteers” describes results from an
ongoing phase 1 study led by Roderick B. Ellis-Pegler and Christian Schwabe of Auckland Clinical Studies Ltd, Auckland, New Zealand
and a group of researchers from Achillion.
Across all four groups, ACH-4471 achieved peak plasma concentrations between 1 and 2.5 hours after oral dosing. Up
to 100% inhibition of complement activity was achieved in all dose groups, and duration of inhibition was dose dependent. In
addition, Group 4, which evaluated 1,200 mg of ACH-4471 given every twelve hours for 2 doses, achieved a median 99.5% inhibition
(range 96 – 100%) of hemolysis at 24 hours.
"We are very encouraged by these data, which support our focus on developing potent, specific factor D inhibitor
compounds, including ACH-4471, as a potentially novel approach to treating alternative pathway complement-mediated diseases such as
PNH and C3G,” commented Milind Deshpande, Ph.D., President and Chief Executive Officer of Achillion. “Achieving sustained
suppression of AP activity, as measured by the AP hemolysis and Wieslab assays, combined with modeling from these interim study
results, suggest the potential for twice daily dosing to achieve sustained inhibition of AP activity."
Study Design and Key Findings
The phase 1 study, initiated in February 2016, aims to assess the safety and tolerability of single ascending oral doses of
ACH-4471 in healthy volunteers and to evaluate its pharmacokinetic (PK) and pharmacodynamic (PD) profile and PK/PD relationship as
measured by the serum alternative pathway (AP) activity ex vivo.
In the study, 36 subjects have been dosed and evaluated. Trial participants were assigned to one of four groups:
- Group 1: 200 mg, single dose (6 active + 6 placebo subjects)
- Group 2: 600 mg, single dose (6 active + 2 placebo subjects)
- Group 3: 1200 mg, single dose (6 active + 2 placebo subjects)
- Group 4: 1200 mg x 2 doses (Q12H) (6 active + 2 placebo subjects)
For all groups, inhibition of serum AP activity was evaluated using the AP Wieslab and hemolysis assays. Blood samples were
collected from days 1 through 7 to determine plasma concentrations. Trial participants were monitored through the last scheduled
visit at day 28 for any adverse events.
The interim study data indicate ACH-4471 was well-tolerated at all dose levels examined with no safety trends noted. Evaluation
of serum AP activity by ex vivo assessment suggests rapid inhibition of AP activity after oral dosing. Furthermore, the
concentrations of Bb, the cleavage product of factor B by factor D, were determined for the assessment of the inhibitory effect of
ACH-4471 on in vivo factor D activity. Bb levels were shown to decline after dosing with ACH-4471 with the lowest Bb
levels observed at 16 hours post-dosing in Groups 3 and 4 and a gradual return to baseline by 48 hours after dosing.
Achillion plans to begin dosing in a phase 1 multiple-ascending dose study evaluating 14-days of dosing in healthy volunteers in
June. The Company is also planning to initiate phase 2 studies of ACH-4471 in two complement-mediated diseases, PNH and C3G, by the
end of 2016.
Abstracts for the 2016 Congress of the European Hematology Association are available online and can be accessed at
http://www.ehaweb.org/. A reprint of the late breaking poster presentation will be available from the Resources section of the
Achillion website at http://www.achillion.com.
About the Achillion Complement Factor D Platform
Achillion has leveraged its internal discovery capabilities and a novel complement-related platform to develop
drug candidates that are oral inhibitors of complement factor D. Factor D is an essential serine protease involved in the
complement pathway, a part of the innate immune system. Achillion's complement platform is focused on seeking to advance small
molecule compounds that inhibit factor D and can potentially be used in the treatment of immune-related diseases in which
complement plays a critical role. Potential indications being evaluated for these compounds include paroxysmal nocturnal
hemoglobinuria (PNH), C3 Glomerulopathy (C3G), dry age-related macular degeneration (dry AMD), and chronic obstructive pulmonary
disease (COPD). Achillion anticipates that its platform could play a role in addressing the needs of all PNH patients, including
patients who have suboptimal response to, or fail to respond to, the currently available treatments, as well as for patients
suffering from other alternative pathway complement-mediated diseases. Achillion nominated ACH-4471 for clinical development in
December 2015, and initiated clinical development in February 2016.
About Achillion Pharmaceuticals
Achillion Pharmaceuticals, Inc. (NASDAQ:ACHN) is a science-driven, patient-focused company seeking to leverage
its strengths across the continuum from discovery to commercialization in its goal of providing better treatments for people with
serious diseases. The company employs a highly-disciplined discovery and development approach that has allowed it to pursue
best-in-class oral antiviral therapy for chronic hepatitis C (HCV) and build a platform of potent and specific complement
inhibitors. Achillion is rapidly advancing its efforts to become a fully-integrated pharmaceutical company with a goal of bringing
life-saving medicines to patients with rare diseases. More information is available at http://www.achillion.com.
Cautionary Note Regarding 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 important factors that could cause actual results to differ
materially from those indicated by such forward-looking statements. Achillion may use words such as “expect,” “anticipate,”
“project,” “intend,” “plan,” “aim,” “believe,” “seek,” “ estimate,” “can,” “focus,” “will,” “look forward,” “goal,” and “may” and
similar expressions to identify such forward-looking statements. These forward-looking statements also include statements about:
the potential for the Company’s complement factor D inhibitor compounds, including ACH-4471, to serve as a novel approach to
treating alternative pathway complement-mediated diseases such as PNH and C3G; the potential for the ACH-4471 data to inform future
trials and study protocols; the Company’s development plans and timelines for ACH-4471; The Company’s belief that its platform
could play a role in addressing the needs of specified types of patients; and statements regarding the Company’s plans, prospects
and strategies. Among the important 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 studies
any favorable findings in preclinical or early-stage healthy volunteers studies of ACH-4471; advance the preclinical and clinical
development of its complement factor D inhibitors under the timelines it projects in current and future preclinical studies and
clinical trials; obtain and maintain patent protection for its drug candidates and the freedom to operate under third party
intellectual property; demonstrate in any current and future clinical trials the requisite safety, efficacy and combinability of
its drug candidates; obtain and maintain necessary regulatory approvals; establish commercial manufacturing arrangements; identify,
enter into and maintain collaboration agreements with third-parties; compete successfully in the markets in which it seeks to
develop and commercialize its product candidates and future products; manage expenses; manage litigation; raise the substantial
additional capital needed to achieve its business objectives; and successfully execute on its business strategies. These and other
risks are described in the reports filed by Achillion with the U.S. Securities and Exchange Commission, including its Quarterly
Report on Form 10-Q for the fiscal quarter ended March 31, 2016, 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 duty to update any forward-looking statement, except as required by applicable law.
Investors: Glenn Schulman Senior Director, Investor Relations Achillion Pharmaceuticals, Inc. Tel. (203) 624-7000 gschulman@achillion.com Media: Liz Power Senior Director, Public Relations Achillion Pharmaceuticals, Inc. Tel: (203) 752-5509 lpower@achillion.com
