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
provided comment on the Ocaliva (obeticholic acid or OCA) Dear
Healthcare Provider (DHCP) letter issued on September 12, 2017, and
the subsequent drug safety communication issued by the U.S. Food
and Drug Administration (FDA) on September 21, 2017.
Ocaliva was approved in the U.S. in May 2016 (and subsequently
in the European Union and Canada) for the treatment of patients
with primary biliary cholangitis (PBC) with an inadequate response
to, or intolerant of the standard of care, UDCA. PBC is a rare and
life-threatening progressive liver disease that primarily afflicts
women and is a leading cause of liver failure with resulting need
for liver transplant in women. Ocaliva therefore represents an
important treatment option for patients with PBC and since its
approval more than 3,000 patients have been treated with Ocaliva in
the U.S. alone. More than 150 patients are enrolled in ongoing open
label phases of Intercept’s Phase 2 and Phase 3 clinical trials and
have been on OCA treatment for periods ranging from approximately
three to seven years.
Label Recommended Ocaliva DosingRecommended
dosing in the label for Ocaliva in earlier stage PBC patients with
no or mild hepatic impairment (non-cirrhotic or Child-Pugh A
cirrhosis) starts at 5 mg once daily, increasing after three months
to 10 mg once daily based on tolerability and treatment response.
However, in late stage patients with moderate or severe hepatic
impairment (Child Pugh B or C cirrhosis), recommended dosing starts
at 5 mg once weekly, with the possibility to gradually increase to
a maximum of 10 mg twice weekly. The reason for this less frequent
dosing is that systemic and hepatic concentrations of Ocaliva are
predicted to significantly increase in such patients and
dose-related liver adverse reactions have previously been
documented in PBC patients participating in clinical trials.
Recently Issued Dear Healthcare Provider Letter and FDA
Safety CommunicationIn the course of Intercept’s
post-marketing pharmacovigilance activities, deaths have been
reported in PBC patients with moderate or severe hepatic impairment
(Child Pugh B or C cirrhosis). In an analysis performed by
Intercept and in consultation with the FDA, Intercept concluded
that these patients were prescribed once daily doses of Ocaliva,
which is seven times higher than the recommended weekly dose in
such patients. As a result, Intercept issued the DHCP letter and
the FDA subsequently issued their own safety communication to
reinforce recommended label dosing. Both communications remind
healthcare providers of the importance of the recommended reduced
dosing of Ocaliva in PBC patients with moderate or severe hepatic
impairment (Child Pugh B or C cirrhosis), while reiterating the
importance of close monitoring of PBC patients for progression of
their disease and the occurrence of liver-related adverse
reactions.
Actions to Enhance Education About Appropriate Use of
OcalivaPatient safety is Intercept’s highest priority and
it is imperative that Ocaliva is dosed according to its approved
label. In addition to the DHCP letter, Intercept has taken actions
to enhance education about appropriate use of Ocaliva. These
initiatives include:
- reeducating physicians on the label, with a focus on ensuring
appropriate dosing for patients with moderate or severe hepatic
impairment (Child Pugh B or C cirrhosis);
- enhancing monitoring of patients for liver-related adverse
reactions; and
- completing adjudication of all reported cases of serious liver
injury, including in patients with no or mild hepatic
impairment.
Pursuant to the FDA’s safety communication, Intercept has begun
working with the FDA on updates to the label to better ensure
appropriate and safe use of Ocaliva.
Conference Call at 8:30 a.m.
ET
Intercept will discuss the FDA statement on a
conference call and webcast today at 8:30 a.m. ET. The live event
will be available on the investor page of Intercept's website at
http://ir.interceptpharma.com or by calling (855) 232-3919
(toll-free domestic) or (315) 625-6894 (international) five minutes
prior to the start time (no passcode is required). A replay of the
call will be available on Intercept's website approximately two
hours after the completion of the call and will be archived for two
weeks.
About
Ocaliva® (obeticholic
acid)
Ocaliva is indicated in the United States for the treatment of
primary biliary cholangitis (PBC) in combination with
ursodeoxycholic acid (UDCA) in adults with an inadequate response
to UDCA, or as monotherapy in adults unable to tolerate UDCA.
This indication is approved under accelerated approval based on
a reduction in alkaline phosphatase (ALP), as a surrogate endpoint
which is reasonably likely to predict clinical benefit, including
an improvement in liver transplant free-survival. 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. Intercept is currently enrolling COBALT, a Phase 4 clinical
outcomes trial of Ocaliva in patients with PBC with the goal of
confirming clinical benefit on a post-marketing basis.
In December 2016, Ocaliva received conditional marketing
authorization in Europe for the treatment of PBC in combination
with UDCA in adults with an inadequate response to UDCA or as
monotherapy in adults unable to tolerate UDCA, conditional to the
company providing further data post-approval to confirm benefit.
For detailed safety information for Ocaliva 5 mg and 10 mg tablets
including posology and method of administration, special warnings,
drug interactions and adverse drug reactions, please see the
European Summary of Product Characteristics that can be found
on www.ema.europa.eu.
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 (HDLC). 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 the U.S. Full Prescribing Information for
Ocaliva (obeticholic acid) 5 mg and 10 mg tablets.
About InterceptIntercept 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), 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.
CONTACT: For more
information about Intercept Pharmaceuticals, please
contact:
Intercept Pharmaceuticals:Mark
Vignola+1-646-747-1000investors@interceptpharma.com
Media inquiries: media@interceptpharma.com
Investor inquiries:
investors@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 on the commercial
potential of Ocaliva, Intercept’s review and analysis of the cases
reported by the FDA and the results thereof, any future events that
may be experienced by patients who use Ocaliva and the association
of such events with its use, the results of Intercept’s educational
efforts with healthcare providers and other planned and ongoing
initiatives, Intercept’s continuing interactions with the FDA, the
changes to the label for Ocaliva that may result from Intercept’s
discussions and negotiations with the FDA and the impact thereof,
including in relation to the commercial potential of Ocaliva,
Intercept’s ongoing and future clinical development programs and
any impact thereto, 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: the potential
benefit and commercial potential of Ocaliva in PBC, and Intercept's
ability to maintain its regulatory approval in jurisdictions in
which Ocaliva is approved for use 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 ones in which it is approved
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
products and 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 products and 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 products and
product candidates; Intercept's ability to successfully
commercialize its products and product candidates; the size and
growth of the markets for Intercept's products and 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 received from payors; the
success of competing drugs that are or become available; regulatory
developments in the United States and other countries; the
performance of third-party suppliers and manufacturers; 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; Intercept's need for and ability to
obtain additional financing; Intercept's estimates regarding
expenses, revenues and capital requirements and the accuracy
thereof; Intercept's use of cash and short-term investments;
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, 2016 filed on March 1, 2017 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.
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