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 multiple new analyses supporting the use of routine
noninvasive tests (NITs) to identify patients with advanced
fibrosis due to NASH and measure obeticholic acid (OCA) treatment
response. The new analyses, which include an oral presentation of
REGENERATE interim analysis data showing that OCA helped patients
achieve marked improvements in key noninvasive measures of liver
fibrosis, are being presented at The Liver Meeting Digital
Experience™, the Annual Meeting of the American Association for the
Study of Liver Diseases (AASLD), which will be held virtually from
November 13, 2020 to November 16, 2020.
“NITs are rapidly replacing liver biopsy for identifying and
monitoring patients with advanced fibrosis due to NASH in routine
clinical practice, and this year’s Liver Meeting features a wealth
of new data reinforcing the value of noninvasive strategies to
manage patients treated with OCA,” said Naim Alkhouri, M.D., Chief
of Transplant Hepatology, and Director of the Fatty Liver Program
at Arizona Liver Health in Phoenix. “Using a simple, sequential
algorithm with two common NITs, we were able to identify a
higher-risk subgroup of patients with fibrosis due to NASH and
evaluate their treatment response noninvasively; these patients
achieved marked reductions in measures of liver biochemistry and
liver stiffness as assessed by transient elastography through 18
months of treatment.”
As previously reported, once-daily OCA 25 mg met the primary
composite endpoint of fibrosis improvement (≥1 stage) with no
worsening of NASH at the planned 18-month interim analysis of the
Phase 3 REGENERATE study with high statistical significance
(p=0.0002 vs. placebo). The new post hoc analysis being presented
at The Liver Meeting evaluated the NIT-based efficacy of OCA in
patients from the intent-to-treat population of the REGENERATE
interim analysis who had Fibrosis-4 (FIB-4) and transient
elastography data available at baseline. FIB-4 and transient
elastography were applied sequentially to categorize patients’
fibrosis severity; patients with possible advanced fibrosis
(indeterminant status) or advanced fibrosis were pooled (OCA 25 mg,
n=266; placebo, n=277). At month 18, OCA reduced mean alanine
aminotransferase (ALT) scores and median transient elastography
scores by 50.1% and 25.6%, respectively; reductions for placebo
were 30.2% and 4.2%, respectively, suggesting that such noninvasive
assessments can be utilized to monitor fibrosis improvement in
OCA-treated patients.
Additional Analyses Support the Role of
NITs for Management of Advanced Fibrosis Due to NASH
Multiple additional analyses being presented at the virtual
Liver Meeting reinforce the value of noninvasive strategies for
managing patients with advanced fibrosis due to NASH:
- In an oral presentation (Abstract 56), an analysis of more than
4,000 patients screened for the REGENERATE study found that
application of two sequential NITs improved the accuracy of
identification and reduced misclassification of disease as compared
to two simultaneous NITs. The authors concluded that sequential NIT
strategies may decrease the need for liver biopsy, while
maintaining the accuracy of diagnosis in patients with advanced
fibrosis due to NASH.
- An analysis (Abstract 1589) comparing FIB-4, liver stiffness
measurement by transient elastography, and liver biopsy to predict
the incidence of liver-related outcomes (e.g., cirrhosis
complications and/or hepatocellular carcinoma) in patients with
nonalcoholic fatty liver disease concluded that the predictive
accuracy of FIB-4 and transient elastography is similar to that of
liver biopsy for predicting liver-related events.
- A review (Abstract 1576) of data from a large U.S. claims
database that included approximately 21,500 patients diagnosed with
NASH who met the study’s inclusion criteria found that only 11% had
a liver biopsy, underscoring the fact that liver biopsy is
infrequently performed in the real world clinical practice
setting.
“Strong collaboration among patient groups, academic centers and
industry, coupled with large datasets from Phase 3 clinical trials
have accelerated our ability to identify and validate noninvasive
alternatives to biopsy for our patients with fibrosis due to NASH,”
said Jerome Boursier, M.D., Ph.D., professor of Medicine,
Hepato-Gastroenterology Department of Angers University Hospital,
and head of HIFIH laboratory, Angers University in France. “The new
NIT data from the interim analysis of the REGENERATE study being
presented at the Liver Meeting represent a major step forward.
Clearly, the field is coalescing around a sequential testing
strategy that combines two commonly used NITs; this approach
addresses the major limitations of liver biopsy because it is both
scalable and patient-friendly without appearing to sacrifice
predictive accuracy. Sequential use of NITs starting with a simple
test confirmed by a specialized one will also help to organize and
optimize the patient pathway.”
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. In the United States, NASH is currently the
second leading cause for liver transplantation overall, and in
females, the leading cause. NASH is anticipated to become the
leading indication for liver transplantation in Europe within the
next decade. There are currently no medications approved for the
treatment of NASH.
About the REGENERATE Study
REGENERATE is a Phase 3, randomized, double-blind,
placebo-controlled, multicenter study assessing the safety and
efficacy of obeticholic acid (OCA) on clinical outcomes in patients
with liver fibrosis due to NASH, an investigational use. A
pre-specified 18-month interim analysis was conducted to assess the
effect of OCA on liver histology comparing month 18 biopsies with
baseline. The intent-to-treat population for the interim analysis
included 931 patients with stage 2 and 3 fibrosis (placebo, n=311;
OCA 10 mg, n=312; OCA 25 mg, n=308). REGENERATE has completed
target enrollment for the clinical outcomes cohort, with 2,480
adult NASH patients randomized at 339 qualified centers worldwide,
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 its long-term
safety.
The safety population of the interim analysis included 1,968
randomized patients who received at least one dose of
investigational product (OCA or placebo) with exposures up to 37
months. Adverse events were generally mild to moderate in severity
and the most common were consistent with the known profile of OCA.
The frequency of serious adverse events was similar across
treatment arms (11% in placebo, 11% in OCA 10 mg and 14% in OCA 25
mg), and no serious adverse event occurred in > 1% of patients
in any treatment group. There were 3 deaths in the study (2 in
placebo: bone cancer and cardiac arrest and 1 in OCA 25 mg:
glioblastoma) and none were considered related to treatment. The
most common adverse event reported was dose-related pruritus
(placebo, 19%; OCA 10 mg, 28%; OCA 25 mg, 51%). The large majority
of pruritus events were mild to moderate, with severe pruritus
occurring in a small number of patients (< 1% in placebo, <
1% in OCA 10 mg and 5% in OCA 25 mg). A higher incidence of
pruritus-associated treatment discontinuation was observed for OCA
25 mg (< 1% in placebo, < 1% in OCA 10 mg, and 9% in OCA 25
mg). Consistent with observations from previous NASH studies, OCA
treatment was associated with an increase in low density
lipoprotein (LDL) cholesterol, with a peak increase of 22.6 mg/dL
at 4 weeks and subsequently reversing and approaching baseline at
month 18 (4.0 mg/dL increase from baseline). Triglycerides rapidly
and continually decreased in the OCA treatment groups through month
18. There were few and varied serious cardiovascular events and
incidence was balanced across the three treatment groups (2% in
placebo, 1% in OCA 10 mg and 2% in OCA 25 mg). In patients with
type 2 diabetes, OCA treatment was associated with an early
transient increase in glucose and hemoglobin A1c with a return to
levels similar to placebo by month 6. No clinically meaningful
changes were noted in non-diabetic patients. With respect to
hepatobiliary events, more patients (3%) on OCA 25 mg experienced
gallstones or cholecystitis compared to <1% on placebo and 1% on
OCA 10 mg. While hepatic serious adverse events were rare (<1%
incidence in each of the three treatment groups), more occurred in
the OCA 25 mg group with no pattern attributable to OCA.
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). Founded
in 2002 in New York, Intercept has operations in the
United States, Europe and Canada. For more
information, please visit www.interceptpharma.com or connect with
the company on Twitter and LinkedIn.
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 clinical trials, including our clinical
trials for the treatment of nonalcoholic steatohepatitis (“NASH”),
the safety and efficacy of our approved product, Ocaliva
(obeticholic acid or “OCA”) for primary biliary cholangitis
(“PBC”), and our product candidates, including OCA for liver
fibrosis due to NASH, the timing and acceptance of our regulatory
filings and the potential approval of OCA for liver fibrosis due to
NASH, the review of our New Drug Application for OCA for the
treatment of liver fibrosis due to NASH by the U.S. Food and Drug
Administration (FDA), our intent to work with the FDA to address
the issues raised in the complete response letter (CRL), the
potential commercial success of OCA, as well as our strategy,
future operations, future financial position, future revenue,
projected costs, financial guidance, 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: our ability to successfully
commercialize Ocaliva for PBC; our ability to maintain our
regulatory approval of Ocaliva for PBC in the United
States, Europe, Canada, Israel, Australia and
other jurisdictions in which we have or may receive marketing
authorization; 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 liver fibrosis due
to NASH following the issuance of the CRL by the FDA; any advisory
committee recommendation or dispute resolution determination
that our product candidates, including OCA for liver fibrosis due
to 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 liver fibrosis due to 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 liver
fibrosis due to 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 liver
fibrosis due to 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; 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 in the
jurisdictions in which we intend to seek approval or completing and
timely reporting the results of our NASH or PBC 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
liver fibrosis due to 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 liver fibrosis due to 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 liver fibrosis due to
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
liver fibrosis due to 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 prevent system failures, data breaches or violations of 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 and
short-term investments; our ability to acquire, license and invest
in businesses, technologies, product candidates and products; our
ability to attract and retain key personnel to manage our business
effectively; our ability to manage the growth of our operations,
infrastructure, personnel, systems and controls; our ability to
obtain and maintain adequate insurance coverage; the impact of
COVID-19, including any impact on our results of operations or
financial position, related quarantines and 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, facility closures or other restrictions, and the extent
and duration thereof; the impact of general U.S. and
foreign economic, industry, market, regulatory or political
conditions, including the potential impact of Brexit; and the other
risks and uncertainties identified in our periodic filings filed
with the U.S. Securities and Exchange Commission, including
our Annual Report on Form 10-K for the year ended December 31,
2019 and our Quarterly Report on Form 10-Q for the quarter ended
September 30, 2020.
Contact
For more information about Intercept, please contact:
Lisa DeFrancesco+1-646-565-4833investors@interceptpharma.com
Christopher Frates+1-646-757-2371media@interceptpharma.com
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