Intercept Pharmaceuticals Receives Positive CHMP Opinion for
Ocaliva® (Obeticholic Acid) for the Treatment of Primary Biliary
Cholangitis in the European Union
NEW YORK, Oct. 14, 2016 (GLOBE
NEWSWIRE) -- Intercept Pharmaceuticals, Inc. (Nasdaq:ICPT)
(Intercept), a biopharmaceutical company focused on the development
and commercialization of novel therapeutics to treat non-viral,
progressive liver diseases, today announced that the European
Medicines Agency's (EMA) Committee for Medicinal Products for Human
Use (CHMP) adopted a positive opinion recommending marketing
authorization of the Company's Marketing Authorization Application
(MAA) for obeticholic acid (OCA), an FXR agonist, for the treatment
of primary biliary cholangitis (PBC) conditional to the company
providing further data post-approval to confirm benefit.
Ursodeoxycholic acid (UDCA) is
currently the only approved medication for the treatment of PBC in
Europe and is the standard of care for all PBC patients. However, a
substantial percentage of patients treated with UDCA continue to
experience persistent elevations above the upper limit of normal in
the serum marker alkaline phosphatase (ALP), which has been shown
to correspond with increased risk of liver failure, need for liver
transplant and death. Patients with PBC also face a risk of
experiencing adverse outcomes when bilirubin levels are elevated.
Total bilirubin levels, even within the normal range, have been
shown to predict clinical outcomes in PBC.
"Although it is a rare disease, PBC
remains one of the most common indications for liver transplant
among women in Europe," said David Jones, M.D., Ph.D., Professor of
Liver Immunology at Newcastle University and Consultant
Hepatologist at Newcastle upon Tyne Hospitals Trust, which hosts
one of Europe's leading clinical services in the disease. "There is
substantial unmet need in this disease and a real urgency around
the need for new therapies to help the many PBC patients who are
either intolerant of the single existing approved therapy
ursodeoxycholic acid or don't respond to it sufficiently to protect
their livers and prevent the development of cirrhosis and the need
for transplant."
The MAA submission included data from
more than 1,500 subjects exposed to at least a single dose of OCA.
The positive opinion of the CHMP was based on efficacy and safety
data derived from three randomized double-blind, placebo-controlled
clinical trials in patients with PBC evaluating the effect of OCA
on ALP and bilirubin. The MAA submission was also supported by two
clinical databases that include more than 10,000 patients from the
Global PBC Study Group and UK-PBC Group, both independently
confirming that achieving lower ALP and/or bilirubin levels is
significantly correlated with increased transplant-free
survival.
The CHMP opinion will form the basis
for a European Commission (EC) decision as to whether to formally
grant the conditional marketing authorization for OCA with unified
labelling in the 28 countries that are Member States of the
European Union, as well as European Economic Area members Iceland,
Liechtenstein and Norway. As the conditions for approval, Intercept
is required to provide post-approval updates on safety and efficacy
analyses for OCA from the ongoing COBALT outcomes trial and a
short-term trial in patients with hepatic impairment.
"We owe a tremendous debt to the many
patients and physicians whose participation in the research program
for OCA led to this positive outcome," said Lisa Bright,
Intercept's President, International. "In addition to playing a
critical role in the development of OCA, the PBC community in
Europe has been the driving force in establishing the two major
patient databases that have been so central to recent advances in
our understanding of the disease. There is a palpable sense of
excitement about the growth of PBC awareness in Europe, and the
CHMP's positive opinion on OCA brings us one step closer to
introducing the first new therapy for PBC in approximately two
decades."
About Primary
Biliary Cholangitis
Primary biliary cholangitis (PBC) is a rare, autoimmune cholestatic
liver disease that puts patients at risk for life-threatening
complications. PBC is primarily a disease of women, afflicting
approximately one in 1,000 women over the age of 40. If left
untreated, survival of PBC patients is significantly worse than the
general population.
About
Obeticholic Acid (OCA)
Obeticholic acid is an agonist of the farnesoid X receptor (FXR), a
nuclear receptor expressed in the liver and intestine. FXR is a key
regulator of bile acid, inflammatory, fibrotic and metabolic
pathways.
May 2016, the U.S. Food and Drug
Administration (FDA) granted accelerated approval to obeticholic
acid for the treatment of PBC under the brand name
Ocaliva® based on a reduction in ALP. An improvement in
survival or disease-related symptoms has not been established.
Continued approval for this indication may be contingent upon
verification and description of clinical benefit in confirmatory
trials. The brand name Ocaliva has been provisionally approved by
the EMA.
U.S. IMPORTANT
SAFETY INFORMATION
Contraindications
Ocaliva is contraindicated in patients with complete biliary
obstruction.
Warnings and
Precautions
Liver-Related
Adverse Reactions
In two 3-month, placebo-controlled clinical trials, a dose-response
relationship was observed for the occurrence of liver-related
adverse reactions including jaundice, ascites and primary biliary
cholangitis flare with dosages of Ocaliva of 10 mg once daily to 50
mg once daily (up to 5-times the highest recommended dosage), as
early as one month after starting treatment with Ocaliva.
In a pooled analysis of three
placebo-controlled trials in patients with PBC, the
exposure-adjusted incidence rates for all serious and otherwise
clinically significant liver-related adverse reactions, and
isolated elevations in liver biochemical tests, per 100 patient
exposure years (PEY) were: 5.2 in the Ocaliva 10 mg group
(highest recommended dosage), 19.8 in the Ocaliva 25 mg group (2.5
times the highest recommended dosage) and 54.5 in the Ocaliva
50 mg group (5 times the highest recommended dosage) compared
to 2.4 in the placebo group.
Monitor patients during treatment
with Ocaliva for elevations in liver biochemical tests and for the
development of liver-related adverse reactions. Weigh the potential
risks against the benefits of continuing treatment with Ocaliva in
patients who have experienced clinically significant liver-related
adverse reactions. The maximum recommended dosage of Ocaliva is 10
mg once daily. Adjust the dosage for patients with moderate or
severe hepatic impairment.
Discontinue Ocaliva in patients who
develop complete biliary obstruction.
Severe
Pruritus
Severe pruritus was reported in 23% of patients in the Ocaliva 10
mg arm, 19% of patients in the Ocaliva titration arm and 7% of
patients in the placebo arm in the POISE trial, a 12-month
double-blind randomized controlled trial of 216 patients. Severe
pruritus was defined as intense or widespread itching, interfering
with activities of daily living, or causing severe sleep
disturbance, or intolerable discomfort, and typically requiring
medical interventions. In the subgroup of patients in the
Ocaliva titration arm who increased their dosage from 5 mg once
daily to 10 mg once daily after 6 months of treatment (n=33), the
incidence of severe pruritus was 0% from months 0 to 6 and 15% from
months 6 to 12. The median time to onset of severe pruritus was 11,
158 and 75 days for patients in the Ocaliva 10 mg, Ocaliva
titration and placebo arms, respectively.
Management strategies include the
addition of bile acid resins or antihistamines, Ocaliva dosage
reduction and/or temporary interruption of Ocaliva dosing.
Reduction in
HDL-C
Patients with PBC generally exhibit hyperlipidemia characterized by
a significant elevation in total cholesterol primarily due to
increased levels of high density lipoprotein-cholesterol (HDL-C).
In the POISE trial, dose-dependent reductions from baseline in mean
HDL-C levels were observed at 2 weeks in Ocaliva-treated patients,
20% and 9% in the 10 mg and titration arms, respectively, compared
to 2% in the placebo arm. At month 12, the reduction from baseline
in mean HDL-C level was 19% in the Ocaliva 10 mg arm, 12% in the
Ocaliva titration arm and 2% in the placebo arm. Nine patients in
the Ocaliva 10 mg arm and six patients in the Ocaliva titration
arm, versus three patients in the placebo arm, had reductions in
HDL-C to less than 40 mg/dL.
Monitor patients for changes in serum
lipid levels during treatment. For patients who do not respond to
Ocaliva after one year at the highest recommended dosage that can
be tolerated (maximum of 10 mg once daily), and who experience a
reduction in HDL-C, weigh the potential risks against the benefits
of continuing treatment.
Adverse
Reactions
The most common adverse reactions from subjects taking Ocaliva
(greater than or equal to 5%) were pruritus, fatigue, abdominal
pain and discomfort, rash, oropharyngeal pain, dizziness,
constipation, arthralgia, thyroid function abnormality and
eczema.
Drug
Interaction
Bile Acid Binding Resins
Bile acid binding resins such as cholestyramine, colestipol or
colesevelam absorb and reduce bile acid absorption and may reduce
the absorption, systemic exposure and efficacy of Ocaliva. If
taking bile acid binding resins, take Ocaliva at least 4 hours
before or 4 hours after (or at as great an interval as possible)
taking a bile acid binding resin.
Please see Full Prescribing
Information for Ocaliva (obeticholic acid) 5 mg and 10 mg
tablets.
About Intercept
Intercept is a biopharmaceutical company focused on the development
and commercialization of novel therapeutics to treat non-viral,
progressive liver diseases, including primary biliary cholangitis
(PBC), nonalcoholic steatohepatitis (NASH), primary sclerosing
cholangitis (PSC) and biliary atresia. Founded in 2002 in New York,
Intercept now has operations in the United States, Europe and
Canada. For more information about Intercept, please
visit www.interceptpharma.com.
Safe Harbor Statements
This press release contains "forward-looking statements" within the
meaning of the Private Securities Litigation Reform Act of 1995,
including, but not limited to, statements regarding the
clinical relevance and utility of ALP and the surrogate endpoint
used in the Phase 3 POISE trial to predict clinical outcomes, the
acceptance of Ocaliva® (obeticholic acid) as a treatment for
PBC by healthcare providers, patients and payors, the
potential approval of OCA in PBC by the European Commission and
other regulatory bodies and the timelines related thereto, the
availability of OCA for the treatment of PBC in Europe and
other jurisdictions outside the United States and timelines
related thereto, the anticipated prevalence of and other
epidemiological estimates and market data related to PBC, the
continued development of OCA and Intercept's other product
candidates, and our strategic directives under the caption "About
Intercept." These "forward-looking statements" are based on
management's current expectations of future events and are subject
to a number of important risks and uncertainties that could cause
actual results to differ materially and adversely from those set
forth in or implied by such forward-looking statements. These
risks and uncertainties include, but are not limited to:
Intercept's ability to successfully commercialize Ocaliva in
PBC, and Intercept's ability to maintain its regulatory approval of
Ocaliva in the United States for Ocaliva in PBC; the initiation,
cost, timing, progress and results of Intercept's development
activities, preclinical studies and clinical trials; the timing of
and Intercept's ability to obtain and maintain regulatory approval
of OCA in PBC in countries outside the United States and in
indications other than PBC and any other product candidates it may
develop such as INT-767; conditions that may be imposed by
regulatory authorities on Intercept's marketing approvals for its
product candidates such as the need for clinical outcomes data (and
not just results based on achievement of a surrogate endpoint), and
any related restrictions, limitations, and/or warnings in the label
of any approved product candidates; Intercept's plans to research,
develop and commercialize its product candidates; Intercept's
ability to obtain and maintain intellectual property protection for
its product candidates; Intercept's ability to successfully
commercialize OCA in indications other than PBC and its other
product candidates; the size and growth of the markets for
Intercept's product candidates and its ability to serve those
markets; the rate and degree of market acceptance of any of
Intercept's products, which may be affected by the reimbursement
that it may receive for its products from payors; the success of
competing drugs that are or become available; the election by
Intercept's collaborators to pursue research, development and
commercialization activities; Intercept's ability to attract
collaborators with development, regulatory and commercialization
expertise; regulatory developments in the United States and other
countries; the performance of third-party suppliers and
manufacturers; Intercept's need for and ability to obtain
additional financing; Intercept's estimates regarding expenses,
future revenues and capital requirements and the accuracy thereof;
Intercept's use of cash, short-term investments and the proceeds
from the offering; Intercept's ability to attract and retain key
scientific or management personnel; and other factors
discussed under the heading "Risk Factors" contained in our annual
report on Form 10-K for the year ended December 31, 2015 filed on
February 29, 2016 as well as any updates to these risk factors
filed from time to time in our other filings with the Securities
and Exchange Commission. All information in this press release is
as of the date of the release, and Intercept undertakes no duty to
update this information unless required by law.
Contact
For more information about Intercept Pharmaceuticals, please contact:
Mark Vignola
+1-646-747-1000
investors@interceptpharma.com
Christopher Frates
+1-646-757-2371
media@interceptpharma.com
This
announcement is distributed by Nasdaq Corporate Solutions on behalf
of Nasdaq Corporate Solutions clients.
The issuer of this announcement warrants that they are solely
responsible for the content, accuracy and originality of the
information contained therein.
Source: Intercept Pharmaceuticals, Inc. via
Globenewswire
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