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Intercept Pharmaceuticals Receives Positive CHMP Opinion for Ocaliva® (Obeticholic Acid) for the Treatment of Primary Biliary Cholangitis in the European Union

Intercept Pharmaceuticals, Inc.
Press release

Intercept Pharmaceuticals Receives Positive CHMP Opinion for Ocaliva®
(Obeticholic Acid) for the Treatment of Primary Biliary Cholangitis in the
European Union

NEW YORK, 2016-10-14 13:35 CEST (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

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

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.


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

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

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

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 (?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

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...

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