Enanta Pharmaceuticals Provides Update on NASH FXR Agonist Programs
October 04 2021 - 7:00AM
Business Wire
– EDP-305 1.0 mg Selected as Optimal Dose
Following ARGON-2 Interim Analysis –
– EDP-297 Not Substantially Differentiated from
EDP-305 Based on Recent Phase 1 Results –
– Company to Discontinue ARGON-2 Trial
Evaluating EDP-305 as a Monotherapy and Prioritize Combination
Approaches for FXR Agonists Through Out-Licensing Strategy –
Enanta Pharmaceuticals, Inc., (NASDAQ: ENTA), a clinical stage
biotechnology company dedicated to creating small molecule drugs
for viral infections and liver diseases, today provides an update
on its two clinical stage farnesoid X receptor (FXR) agonists,
EDP-305 and EDP-297, for the treatment of non-alcoholic
steatohepatitis (NASH). A pre-planned interim analysis of a subset
of patients through week 12 in the Phase 2b ARGON-2 study of
EDP-305 as a monotherapy and data from its Phase 1 clinical study
of EDP-297 provided meaningful information on dose selection and
characterization for these compounds. Enanta has made a business
decision to prioritize combination approaches through an
out-licensing strategy for further development of these two
programs and does not plan to continue further development
internally.
“Looking at a broad range of doses in NASH patients, our interim
analysis of EDP-305 in ARGON-2, in comparison to clinical data from
ARGON-1, indicates that the 1.0 mg dose of EDP-305 provides the
best balance of efficacy and tolerability,” said Jay R. Luly,
Ph.D., President and Chief Executive Officer of Enanta
Pharmaceuticals. “We believe that the multiple mechanisms in
development for NASH today, which reflect the complex
pathophysiology of this disease, make it likely that a combination
approach with FXR agonists will ultimately provide the optimal
treatment regimen for patients. Given this evolving landscape, we
have decided to discontinue the 72-week ARGON-2 study early in
favor of pursuing a combination regimen. Based on the significant
data generated to date, we believe EDP-305, our lead, late-stage
candidate, which has been administered in almost 600 patients for
up to 12 weeks, and EDP-297, our follow-on candidate, are
well-positioned to be an important component of a combination
therapy to bring a much-needed treatment to patients with NASH.
Going forward, we are eager to concentrate our resources on
developing oral drug candidates for treating hepatitis B virus, and
human respiratory diseases including respiratory syncytial virus
and SARS-CoV-2.”
EDP-305 Clinical Update ARGON-2 is a Phase 2b randomized,
double-blind, placebo-controlled, multicenter study evaluating
safety and efficacy of 1.5 mg and 2.0 mg of EDP-305 in patients
with liver biopsy proven NASH. The primary outcome at 72-weeks is
the proportion of subjects who achieve ≥1 stage improvement in
fibrosis without worsening of steatohepatitis and/or resolution of
steatohepatitis and no worsening of liver fibrosis as determined by
liver biopsy. Results from a planned internal interim analysis on a
subset of patients at 12 weeks, as well as review of clinical data
from all tested doses of EDP-305 demonstrated that the 1.0 mg dose
of EDP-305 provides the best balance of efficacy and
tolerability.
ARGON-1 was a 12-week Phase 2a randomized, double-blind,
placebo-controlled study evaluating the safety, tolerability,
pharmacokinetics and efficacy of 1.0 mg and 2.5 mg doses of EDP-305
in a NASH population. The primary objectives of the study were to
evaluate change in ALT levels at week 12 and to evaluate the safety
and tolerability of EDP-305. Key secondary objectives included
change in liver fat content by MRI-PDFF, change in lipids, and
pharmacokinetics and pharmacodynamic parameters, including C4 and
FGF19.
In ARGON-1, EDP-305 1.0 mg dose resulted in good target
engagement as measured by reduction in levels of C4, GGT and ALT
after 12 weeks of treatment. Overall, EDP-305 was generally safe,
with the majority of treatment-emergent adverse events being mild
to moderate. The incidence of treatment discontinuation due to
pruritus was 1.8%.
EDP-297 Clinical Update EDP-297, Enanta’s second FXR
agonist designed for greater potency and tissue targeting, was
evaluated in a Phase 1 randomized, double-blind, placebo-controlled
study which assessed the safety, tolerability and pharmacokinetics
of orally administered single (20-600 microgram) and multiple doses
(5-90 microgram) of EDP-297 in healthy adult subjects. The first
phase assessed single ascending doses of EDP-297 or placebo in
healthy subjects. A "fasted" and "fed" two-part cohort also
assessed food effect. The second phase assessed multiple ascending
doses of EDP-297 or placebo for 14-days in healthy subjects. Each
cohort within each phase enrolled a total of eight subjects who
were randomized to receive EDP-297 or placebo. The cohort assessing
food effect enrolled 10 subjects randomized to receive EDP-297 or
placebo. While strong target engagement was observed at lower doses
of EDP-297, the overall balance of activity and tolerability was
comparable to that of EDP-305. Data from this study will be
submitted for presentation at a future medical conference.
About NASH and FXR Agonists NASH is a serious form of
non-alcoholic fatty liver disease (NAFLD) which is common in the
United States and around the world and is closely associated with
diabetes and obesity. Characterized by an excessive build-up of fat
in the liver causing stress and damage to liver cells, NASH can
lead to inflammation and fibrosis, causing permanent damage,
including cirrhosis and impaired liver function, as well as cancer
and eventually death. NASH is the leading cause of liver
transplants in the United States and Europe and currently has no
FDA-approved treatment. A farnesoid X receptor is a main regulator
of bile acid levels in the liver and small intestine. It responds
to bile acids by regulating gene transcription of key enzymes and
transporters, many of which play important roles in lipid
metabolism, insulin resistance, inflammation and fibrosis. EDP-305
and EDP-297 represent a non-bile-acid FXR agonist class that
contains steroidal and non-steroidal components designed to take
advantage of increased binding interactions with the receptor.
About Enanta Enanta is using its robust, chemistry-driven
approach and drug discovery capabilities to become a leader in the
discovery and development of small molecule drugs for the treatment
of viral infections and liver diseases. Enanta’s research and
development efforts have produced clinical candidates for the
following disease targets: respiratory syncytial virus (RSV),
hepatitis B virus (HBV), SARS-CoV-2 (COVID-19), and non-alcoholic
steatohepatitis (NASH). Enanta is also conducting research in human
metapneumovirus (hMPV).
Enanta’s research and development activities are funded by
royalties from hepatitis C virus (HCV) products developed under its
collaboration with AbbVie. Glecaprevir, a protease inhibitor
discovered by Enanta, is sold by AbbVie in numerous countries as
part of its leading treatment for chronic HCV infection under the
tradenames MAVYRET® (U.S.) and MAVIRET® (ex-U.S.)
(glecaprevir/pibrentasvir). Please visit www.enanta.com for more
information.
Forward Looking Statements Disclaimer This press release
contains forward-looking statements, including statements with
respect to the prospects for out-licensing Enanta’s FXR agonists.
Statements that are not historical facts, are based on management’s
current expectations, estimates, forecasts and projections about
Enanta’s business and the industry in which it operates and
management’s beliefs and assumptions. The statements contained in
this release are not guarantees of future performance and involve
certain risks, uncertainties and assumptions, which are difficult
to predict. Therefore, actual outcomes and results may differ
materially from what is expressed in such forward-looking
statements. Important factors and risks that may affect actual
results include:; the impact of development, regulatory and
marketing efforts of others with respect to competitive treatments
for NASH; the uncertainty of being able to achieve any
out-licensing transaction for an Enanta’s FXR agonist on favorable
terms, if at all ; Enanta’s need to obtain and maintain patent
protection for its product candidates and avoid potential
infringement of the intellectual property rights of others; and
other risk factors described or referred to in “Risk Factors” in
Enanta’s most recent Form 10-Q for the quarter ended June 30, 2021
and other periodic reports filed more recently with the Securities
and Exchange Commission. Enanta cautions investors not to place
undue reliance on the forward-looking statements contained in this
release. These statements speak only as of the date of this
release, and Enanta undertakes no obligation to update or revise
these statements, except as may be required by law.
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version on businesswire.com: https://www.businesswire.com/news/home/20211004005192/en/
Media and Investor Contact Jennifer Viera 617-744-3848
jviera@enanta.com
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