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 positive topline results from a new interim analysis of
its ongoing pivotal Phase 3 REGENERATE trial of OCA in patients
with liver fibrosis due to nonalcoholic steatohepatitis (NASH).
This is the second analysis in which OCA has met the primary
endpoint for the intent-to-treat (ITT) population in REGENERATE and
based on these results, Intercept will be re-submitting its NDA for
OCA in liver fibrosis due to NASH.
In this new interim analysis of the ITT population from
REGENERATE (n=931), 22.4% of subjects randomized to once-daily oral
OCA 25 mg met the primary endpoint of achieving at least one stage
of fibrosis improvement with no worsening of NASH at month 18 on
liver biopsy compared with 9.6% of subjects on placebo
(p<0.0001). These results are consistent with the original
positive analysis announced in February 2019, which also showed
that OCA 25 mg had a statistically significant effect on fibrosis
improvement (p=0.0002). The population in this new interim analysis
mirrored the original analysis population from 2019 but used a
consensus panel approach to histology reads, in line with recent
U.S. Food and Drug Administration (FDA) guidance, while the
original analysis relied on results from individual central
readers. A numerically greater proportion of individuals in the OCA
25 mg treatment group compared to placebo achieved the endpoint of
resolution of NASH with no worsening of liver fibrosis but,
consistent with the original analysis, this did not reach
statistical significance. For the primary objective to be met, the
study was required to achieve only one of the two primary
endpoints.
Safety was evaluated in 2,477 subjects who took at least one
dose of study drug (placebo, OCA 10 mg, or OCA 25 mg). Compared to
the original analysis, the safety population in this new interim
analysis had significantly longer exposure to study drug (median 42
months vs. 15 months), yielding more than 8,000 total patient-years
and 3.4 times more exposure. Nearly 1,000 subjects had been on
study drug for four years.
Treatment-emergent adverse events (TEAEs), treatment-emergent
serious adverse events (TESAEs), and deaths were generally balanced
across the OCA and placebo treatment groups. The most common TEAE
was pruritus (24% in placebo, 33% in OCA 10 mg and 55% in OCA 25
mg) and pruritus was the most common cause for treatment
discontinuation. Serious gallbladder-related events occurred in
<3% of subjects in any treatment group and, consistent with its
known mechanism of action, OCA 25 mg had higher rates of biliary
events including gallstones.
Independent groups of experts reviewed certain categories of
safety events to provide a blinded adjudication as specifically
requested by FDA. These included events pertaining to hepatic
safety (excluding clinical outcomes), cardiovascular and renal.
Topline analysis through four years of treatment showed a
numerically higher number of adjudicated hepatic safety events for
OCA 25 mg, the vast majority of which were mild in severity. For
adjudicated core major adverse cardiovascular events and
adjudicated acute kidney injury events, frequency of events was low
and balanced across treatment groups.
Consistent with its mechanism of action as an FXR agonist, OCA
treatment was associated with an increase in LDL at Month 1 which
returned to near baseline values by Month 12. Changes in other
blood chemistries including ALP (alkaline phosphatase), GGT
(gamma-glutamyl transferase), AST (aspartate aminotransferase), and
ALT (alanine aminotransferase) also showed evidence of FXR mediated
activity, supporting the dose-response of OCA.
“Achieving a statistically significant histology endpoint has
proven to be an extremely high bar in clinical trials for NASH. We
are thrilled that OCA has demonstrated consistent improvement in
fibrosis based on a second methodology and we now have two
positive, statistically significant results for this primary
endpoint from our pivotal REGENERATE trial. These results
demonstrate the antifibrotic effect of OCA and are consistent with
our belief that OCA can be an important treatment for people living
with fibrosis due to NASH,” said Jerry Durso, President and Chief
Executive Officer of Intercept. “The weight of evidence in both
safety and efficacy has notably increased and provides a more
robust benefit:risk profile of OCA. We look forward to our meeting
with FDA later this month to discuss the resubmission of our NDA
for OCA in fibrosis due to NASH.”
Dr. Arun Sanyal, Chair, Division of
Gastroenterology/Hepatology/Nutrition & Director,
Stravitz-Sanyal Liver Institute, VCU Health, Department of Internal
Medicine, said, “Today marks a significant milestone for patients
with fibrosis due to NASH, a disease that currently has no approved
therapy. These data demonstrate that once daily oral OCA has the
potential to improve fibrosis. Further, the safety and tolerability
profile of OCA based on a sizeable dataset should give clinicians
confidence that we are a step closer to a treatment option.”
Analysis Methodology and Efficacy Results
In REGENERATE, patients with biopsy-proven stage 2 or 3 liver
fibrosis due to NASH were randomized 1:1:1 to receive placebo
(n=311), OCA 10 mg (n=312), or OCA 25 mg (n=308) once daily. A
second biopsy was conducted in these 931 subjects at Month 18 for
the planned interim analysis.
The new interim analysis was based on a reassessment of the
baseline and Month 18 liver biopsies using a consensus reading
methodology. Consensus panels were comprised of three
board-certified pathologists who demonstrated accuracy and
reproducibility in their assessments of liver biopsies during
proficiency testing. The consensus panels in this new interim
analysis reviewed digitized whole slide images of the same glass
slides of liver biopsy tissue that were evaluated in the original
analysis using individual central readers.
The results of the new interim analysis from REGENERATE are
shown in the following table:
|
Placebon=311 |
OCA 10 mgn=312 |
OCA 25 mgn=308 |
At least one stage of fibrosis improvement with no worsening of
NASH* |
9.6% |
14.1%p=NS |
22.4%p<0.0001 |
Resolution of NASH‡ with no worsening of liver fibrosis |
3.5% |
6.1%p=NS |
6.5%p=NS |
*Defined as no worsening of hepatocellular ballooning, no worsening
of lobular inflammation and no worsening of steatosis‡Defined as
the overall histopathologic interpretation of (i) no fatty liver
disease or (ii) fatty liver disease (simple or isolated steatosis)
without steatohepatitis AND a nonalcoholic fatty liver disease
(NAFLD) activity score of 0 for ballooning and 0-1 for
inflammation |
Intercept plans to share these data in an upcoming scientific
forum.
OCA has not been approved for the treatment of NASH by any
regulatory authority in any geography and is considered an
investigational treatment for this indication.
About the REGENERATE Study
REGENERATE (Randomized Global Phase 3 Study to Evaluate the
Impact on NASH with Fibrosis of Obeticholic Acid Treatment) is an
ongoing Phase 3, randomized, double-blind, placebo-controlled,
multicenter, international study assessing the safety and efficacy
of obeticholic acid (OCA) on clinical outcomes in patients with
liver fibrosis due to NASH. A pre-specified 18-month interim
analysis was conducted on 931 subjects who had scheduled biopsy at
Month 18 to assess the effect of OCA on liver histology comparing
Month 18 biopsies with baseline biopsies. REGENERATE is fully
enrolled with 2,480 randomized participants and is expected to
continue through clinical outcomes for verification and description
of clinical benefit. The end-of-study analysis will evaluate the
effect of OCA on all-cause mortality and liver-related clinical
outcomes, as well as long-term safety.
About Intercept
Intercept 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.
About Liver Fibrosis due to 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 and death. Advanced fibrosis is associated with a
substantially higher risk of liver-related morbidity and mortality
in patients with NASH. There are currently no medications approved
for the treatment of NASH.
Conference Call on July 7, 2022 at 8:30
a.m. ET
Intercept will hold a conference call to discuss the new data
analysis from its Phase 3 REGENERATE study in patients with liver
fibrosis due to NASH today at 8:30 a.m. ET. The conference call
will be available via a listen-only webcast on the investor page of
our website at http://ir.interceptpharma.com. To join the webcast,
click here. Participants who wish to ask a question may register
here to receive dial-in numbers and a unique PIN to join the call.
While not required, it is recommended you join 10 minutes prior to
the event start. A replay of the call will be available on our
website shortly following the completion of the call and will be
available for one year.
Cautionary Note Regarding Forward-Looking
Statements
This press release contains forward-looking statements,
including, but not limited to, statements regarding:
- The progress, timing, and results of our REGENERATE clinical
trial, including the safety and efficacy of obeticholic acid
(“OCA”) for the treatment of liver fibrosis due to nonalcoholic
steatohepatitis (“NASH”), and the use of a consensus panel
biopsy-reading methodology.
- Our planned New Drug Application (“NDA”) pre-submission meeting
with the FDA regarding OCA for the treatment of liver fibrosis due
to NASH.
- Our planned resubmission of an NDA to the FDA for OCA for the
treatment of liver fibrosis due to NASH, and the potential timing,
review, acceptance, and approval of the NDA.
- The potential commercial success of OCA for NASH, as well as
our strategy, future operations, future financial position, future
revenue, projected costs, prospects, plans, and objectives.
These statements constitute forward-looking statements within
the meaning of Section 27A of the Securities Act of 1933, as
amended, and Section 21E of the Securities Exchange Act of 1934, as
amended. The words “anticipate,” “believe,” “estimate,” “expect,”
“intend,” “may,” “plan,” “predict,” “project,” “target,”
“potential,” “will,” “would,” “could,” “should,” “possible,”
“continue” and similar expressions are intended to identify
forward-looking statements, although not all forward-looking
statements contain these identifying words. Readers are cautioned
not to place undue reliance on these forward-looking statements,
which speak only as of the date of this release, and we undertake
no obligation to update any forward-looking statement except as
required by law. These forward-looking statements are based on
estimates and assumptions by our management that, although believed
to be reasonable, are inherently uncertain and subject to a number
of risks. The following represent some, but not necessarily all, of
the factors that could cause actual results to differ materially
from historical results or those anticipated or predicted by our
forward-looking statements:
- The success of our existing business and operations, including
Ocaliva for PBC.
- Our ability to successfully commercialize Ocaliva for PBC and,
if approved, OCA for NASH.
- Our ability to maintain our regulatory approval of Ocaliva for
PBC.
- Our ability to timely and cost-effectively file for and obtain
regulatory approval of our product candidates on an accelerated
basis or at all, including OCA for NASH.
- Our ability to address the issues raised in the complete
response letter (“CRL”) received in June 2020 with respect to OCA
for NASH.
- Any advisory committee recommendation or dispute resolution
determination that OCA for NASH should not be approved or approved
only under certain conditions.
- Any future determination that the regulatory applications and
subsequent information we submit for our product candidates,
including OCA for NASH, do not contain adequate clinical or other
data or meet applicable regulatory requirements for approval.
- Conditions that may be imposed by regulatory authorities on our
marketing approvals for our products and product candidates,
including OCA for NASH, such as the need for clinical outcomes data
(and not just results based on achievement of a surrogate
endpoint), any risk mitigation programs such as a REMS, and any
related restrictions, limitations and/or warnings contained in the
label of any of our products or product candidates.
- Any potential side effects associated with Ocaliva for PBC, OCA
for NASH, or our other product candidates that could delay or
prevent approval, require that an approved product be taken off the
market, require the inclusion of safety warnings or precautions, or
otherwise limit the sale of such product or product candidate,
including in connection with our update to Ocaliva prescribing
information in May 2021 contraindicating Ocaliva for patients with
PBC and decompensated cirrhosis, a prior decompensation event, or
compensated cirrhosis with evidence of portal hypertension.
- The initiation, timing, cost, conduct, progress, and results of
our research and development activities, preclinical studies and
clinical trials, including any issues, delays or failures in
identifying patients, enrolling patients, treating patients,
retaining patients, meeting specific endpoints, or completing and
timely reporting the results of our NASH or PBC clinical
trials.
- The outcomes of interactions with regulators, including the
FDA, regarding our clinical trials.
- Our ability to establish and maintain relationships with, and
the performance of, third-party manufacturers, contract research
organizations and other vendors upon whom we are substantially
dependent for, among other things, the manufacture and supply of
our products, including Ocaliva for PBC and, if approved, OCA for
NASH, and our clinical trial activities.
- Our ability to identify, develop, and successfully
commercialize our products and product candidates, including our
ability to successfully launch OCA for NASH, if approved.
- Our ability to obtain and maintain intellectual property
protection for our products and product candidates, including our
ability to cost-effectively file, prosecute, defend, and enforce
any patent claims or other intellectual property rights.
- The size and growth of the markets for our products and product
candidates and our ability to serve those markets.
- The degree of market acceptance of Ocaliva for PBC and, if
approved, OCA for NASH or our other product candidates among
physicians, patients, and healthcare payors.
- The availability of adequate coverage and reimbursement from
governmental and private healthcare payors for our products,
including Ocaliva for PBC and, if approved, OCA for NASH, and our
ability to obtain adequate pricing for such products.
- Our ability to establish and maintain effective sales,
marketing, and distribution capabilities, either directly or
through collaborations with third parties.
- Competition from existing drugs or new drugs that become
available.
- Our ability to attract and retain key personnel to manage our
business effectively.
- Our ability to prevent or defend against system failures or
security or data breaches due to cyber-attacks, or cyber
intrusions, including ransomware, phishing attacks and other
malicious intrusions.
- Our ability to comply with data protection laws; costs and
outcomes relating to any disputes, governmental inquiries or
investigations, regulatory proceedings, legal proceedings or
litigation, including any securities, intellectual property,
employment, product liability or other litigation.
- Our collaborators’ election to pursue research, development and
commercialization activities.
- Our ability to establish and maintain relationships with
collaborators with development, regulatory and commercialization
expertise.
- Our need for and ability to generate or obtain additional
financing.
- Our estimates regarding future expenses, revenues and capital
requirements and the accuracy thereof.
- Our use of cash, cash equivalents and short-term
investments.
- Our ability to acquire, license and invest in businesses,
technologies, product candidates and products.
- Our ability to manage the growth of our operations,
infrastructure, personnel, systems and controls.
- Our ability to obtain and maintain adequate insurance
coverage.
- Continuing threats from COVID-19, including additional waves of
infections, and their impacts including quarantines and other
government actions, delays relating to our regulatory applications,
disruptions relating to our ongoing clinical trials or involving
our contract research organizations, study sites or other clinical
partners, disruptions relating to our supply chain or involving our
third-party manufacturers, distributors or other distribution
partners, and facility closures or other restrictions, and impact
of the foregoing on our results of operations and financial
position.
- The impact of general economic, industry, market, regulatory,
or political conditions.
- The other risks and uncertainties identified in our periodic
filings filed with the U.S. Securities and Exchange Commission,
including our latest Annual Report on Form 10-K and/or Quarterly
Report on Form 10-Q.
CONTACT
For 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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