- Results indicate up to 100% inhibition of
alternative-pathway (AP) activity in hemolysis and Wieslab assays
after oral dosing of ACH-4471 -
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
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