Intercept Pharmaceuticals, Inc. (Nasdaq:ICPT), a biopharmaceutical
company focused on the development and commercialization of novel
therapeutics to treat non-viral, progressive liver diseases, today
announced the filing of a New Drug Submission to Health Canada,
seeking Canadian marketing approval for obeticholic acid (OCA) for
the treatment of primary biliary cholangitis, also referred to as
primary biliary cirrhosis (PBC), when used in combination with
ursodeoxycholic acid (UDCA) in adults with an inadequate response
to UDCA or as monotherapy in adults unable to tolerate UDCA.
"Our submission to Health Canada not only reflects
a significant milestone for Intercept, but more importantly for the
estimated 8,000 Canadians living with PBC, many of whom remain at
risk of liver failure and need for transplantation despite the
current standard of care,” said Dr. Mark Pruzanski, President &
CEO of Intercept Pharmaceuticals. “We are pleased with Health
Canada’s decision to grant OCA priority review status, recognizing
the high unmet medical need for new therapies in PBC and the
potential of OCA to offer meaningful benefits in improving outcomes
for patients impacted by the disease.”
PBC is a rare, autoimmune cholestatic liver disease
that puts patients at risk for life-threatening complications. It
is primarily a disease of women, affecting approximately one in
1,000 women over the age of 40. If left untreated, survival of
patients with PBC is significantly worse than that of the general
population.
Canadian researchers have played a significant role
in advancing the clinical research and management of PBC. With
seven clinical trial sites across the country participating in the
OCA PBC clinical development program, Canadian clinicians, patients
and health institutions have made a meaningful contribution to the
development of OCA.
“Both patients and doctors have been looking
forward to new avenues of treatment for PBC patients at risk of
disease progression. We have made great inroads in understanding
what may cause PBC but this has not really impacted patient care -
for a rare disease there are too many patients with PBC waiting for
liver transplantation,” said Dr. Andrew Mason, Director of Research
for the Division of Gastroenterology and Hepatology at the
University of Alberta. “In clinical trials, OCA made a significant
and clinically meaningful impact on lab tests used to monitor
biliary disease, such as alkaline phosphatase and bilirubin.
We are hopeful that OCA will be available soon for our patients
with PBC.”
About Obeticholic Acid
(OCA)Obeticholic acid is an agonist of the farnesoid X
receptor (FXR), a nuclear receptor expressed in the liver and
intestine.
The Canadian New Drug Submission includes a total
of 1,507 subjects exposed to at least a single dose of obeticholic
acid. Of these subjects, 432 were patients with PBC, with 290
treated for at least six months and 232 treated for at least one
year. The key efficacy and safety data are derived from three
randomized double-blind, placebo-controlled clinical trials in
patients with PBC evaluating the effect of obeticholic acid on
alkaline phosphatase (ALP) and bilirubin. All three trials met
their primary endpoints with high statistical significance and
improvements were seen in secondary endpoints including markers of
liver injury, immunity, inflammation and apoptosis. Pruritus
(itching), a common symptom of PBC that is unrelated to disease
stage or outcomes, was the most common side effect observed in
obeticholic acid-treated patients.
The regulatory submission is 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.
In Canada, obeticholic acid is an investigational
agent and has not been approved by Health Canada. In 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. A marketing authorization application for
obeticholic acid for the treatment of PBC was accepted by the
European Medicines Authority (EMA) in June 2015 and is currently
under review. The brand name Ocaliva has been provisionally
approved by the EMA.
U.S. IMPORTANT SAFETY
INFORMATIONContraindicationsOcaliva
is contraindicated in patients with complete biliary
obstruction.
Warnings and
PrecautionsLiver-Related Adverse
ReactionsIn 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 PruritusSevere 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-CPatients 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 ReactionsThe 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 InteractionBile 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.
About Intercept Pharma Canada
Inc.Intercept Pharma Canada Inc. is the Canadian
subsidiary of Intercept Pharmaceuticals, Inc., founded in 2015 and
based in Mississauga, Ontario. Intercept is a proud member of the
Canadian biopharmaceutical community.
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 regulatory
approval and launch of OCA in PBC in Canada and other jurisdictions
outside the United States and the timelines related
thereto, the availability of OCA for the treatment of PBC in
Canada 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
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