Intercept Pharmaceuticals Announces REVERSE Phase 3 Study of Obeticholic Acid (OCA) in Compensated Cirrhosis due to NASH Did Not Meet its Primary Endpoint
September 30 2022 - 7:55AM
Intercept Pharmaceuticals, Inc. (Nasdaq: ICPT), a biopharmaceutical
company focused on the development and commercialization of novel
therapeutics to treat progressive non-viral liver diseases, today
announced that REVERSE, a Phase 3 study evaluating the safety and
efficacy of OCA in patients with compensated cirrhosis due to
nonalcoholic steatohepatitis (NASH), did not meet its primary
endpoint of a ≥ 1-stage histological improvement in fibrosis with
no worsening of NASH following up to 18 months of therapy. No new
safety signals for OCA were observed in this population of patients
with cirrhosis.
REVERSE is one of Intercept’s two Phase 3 studies evaluating
different populations in NASH. The Company’s planned NDA for its
lead indication of liver fibrosis due to NASH will be supported by
positive Phase 3 data from the REGENERATE study and is unaffected
by the efficacy results of REVERSE. The Company is on track to
resubmit its NDA in liver fibrosis due to NASH by the end of the
year.
“Achieving statistical significance on a histology endpoint in
compensated cirrhosis due to NASH has proven to be an extremely
high bar in clinical trials and underscores the importance of
treating liver fibrosis due to NASH before it progresses to
cirrhosis,” said M. Michelle Berrey, M.D., M.P.H., President of
Research & Development and Chief Medical Officer of Intercept.
“We remain confident in the potential role that OCA can play in
liver fibrosis due to NASH and the Intercept team is focused on
resubmitting our NDA in this indication based on the positive Phase
3 REGENERATE data.”
In the REVERSE study of 919 randomized subjects with compensated
cirrhosis due to NASH, 11.1% (p=NS) of subjects who were randomized
to receive once-daily oral OCA 10 mg and 11.9% (p=NS) of subjects
who were randomized to receive OCA 10 mg titrated to 25 mg (OCA
10-to-25 mg) after three months achieved a ≥1-stage improvement in
fibrosis with no worsening of NASH after up to 18 months of
treatment, compared with 9.9% of subjects who received placebo.
Though the REVERSE study did not succeed on the histological
evaluation of the primary endpoint, a positive impact on liver
stiffness as defined by transient elastography was noted in both
OCA 10 mg and OCA 10-to-25 mg arms.
Safety was evaluated in 916 subjects who took at least one dose
of study drug (placebo, OCA 10 mg or OCA 10-to-25 mg).
Treatment-emergent adverse events (TEAEs), treatment-emergent
serious adverse events (TESAEs) and deaths were balanced across all
treatment groups in REVERSE.
The most common TEAE was pruritus (31% in placebo, 41% in OCA 10
mg and 57% in OCA 10-to-25 mg) and pruritus was the most common
reason for treatment discontinuation. Serious gallbladder-related
events were balanced across arms (0.6% in placebo, 1.0% in OCA 10
mg, 1.0% in OCA 10-to-25 mg). Consistent with the known mechanism
of action of FXR-agonists, the OCA 10-to-25 mg arm had a higher
incidence of gallstones.
Independent experts reviewed certain categories of safety events
to provide a blinded adjudication as specifically requested by FDA.
These included events pertaining to hepatic safety, cardiovascular
safety and renal safety. There was a numerical increase in the
number of adjudicated hepatic safety events for the OCA-treated
arms; most were mild in severity and related to biochemical
changes. There were no severe or fatal adjudicated hepatic safety
events in any treatment arm. Frequency of adjudicated kidney events
and adjudicated major cardiac adverse events were balanced across
treatment groups.
Intercept is grateful to the patients and clinicians who
participated in the REVERSE trial. The Company will continue to
work with REVERSE investigators to analyze the data from both the
double-blind portion of the study as well as the open-label
extension phase of REVERSE, and plans to share these data at an
upcoming scientific forum.
About the REVERSE StudyREVERSE was a
randomized, double-blind, placebo-controlled, multicenter Phase 3
study evaluating the safety and efficacy of OCA in NASH patients
with compensated cirrhosis. The primary endpoint was the percentage
of patients with histological improvement in fibrosis by at least
one stage with no worsening of NASH using the NASH Clinical
Research Network (CRN) scoring system after up to 18 months of
treatment. Over 900 patients were randomized in a 1:1:1 ratio to
the three treatment arms: once-daily placebo, OCA 10 mg, or OCA 10
mg for the first three months with titration in accordance with the
study protocol up to OCA 25 mg for the remaining study period.
Patients who successfully completed the double-blind phase of
REVERSE were eligible to enroll in an open-label extension phase of
the study for up to 12 additional months.
About Liver Fibrosis and Cirrhosis due to Nonalcoholic
Steatohepatitis (NASH)Nonalcoholic steatohepatitis (NASH)
is a serious progressive liver disease caused by excessive fat
accumulation in the liver that induces chronic inflammation,
resulting in progressive fibrosis (scarring) that can lead to
cirrhosis, eventual liver failure, cancer or death. There are
currently no medications approved for the treatment of NASH.
About InterceptIntercept is a
biopharmaceutical company focused on the development and
commercialization of novel therapeutics to treat progressive
non-viral liver diseases, including primary biliary cholangitis
(PBC) and nonalcoholic steatohepatitis (NASH). For more
information, please visit www.interceptpharma.com or
connect with the Company on Twitter and LinkedIn.
Forward-Looking StatementsThis press release
contains forward-looking statements (FLS), including regarding
resubmission and timing of Intercept’s new drug application for OCA
for treatment of liver fibrosis due to NASH. Important factors
could cause actual results to differ materially from the FLS. For
example, our resubmission could be delayed or be unsuccessful
because of efficacy, safety, or tolerability concerns, problems
with our clinical studies and their data or methods, or our
inability to address to the satisfaction of the FDA the issues
raised in their complete response letter of June 2020 responding to
our earlier submission.
ContactFor more information about Intercept,
please contact:
For investors:Nareg Sagherian, Executive Director, Global
Investor RelationsInvestors@interceptpharma.com
For media:Karen Preble, Executive Director, Global Corporate
CommunicationsMedia@interceptpharma.com
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