Intercept Pharmaceuticals, Inc. (Nasdaq:ICPT) (Intercept), a
biopharmaceutical company focused on the development and
commercialization of novel therapeutics to treat progressive
non-viral liver diseases, today announced results from three new
exploratory analyses of the Phase 3 POISE trial of Ocaliva®
(obeticholic acid) in patients with primary biliary cholangitis
(PBC). The analyses will be presented at the American Academy for
the Study of Liver Diseases (AASLD) Annual Meeting (The Liver
Meeting®), taking place in Boston, MA from November 11-15.
The POISE trial evaluated the safety and efficacy of once-daily
treatment with Ocaliva in PBC patients with an inadequate
therapeutic response to, or who are unable to tolerate,
ursodeoxycholic acid (UDCA). Of 216 patients randomized to three
treatment arms—placebo, Ocaliva 5 mg titrated to 10 mg or Ocaliva
10 mg—93% continued receiving UDCA.
The first POISE presentation (abstract #209) evaluated the
effects of Ocaliva on non-invasive assessments of liver fibrosis
using both transient elastography (Fibroscan™) and the AST to
Platelet Ratio (APRI). These tests have been shown to be effective
in predicting clinical outcomes in PBC, and Ocaliva-treated
patients experienced improvements in both compared with those
receiving placebo. In patients with transient elastography
assessments at baseline and month 12 (approximately 43% of the
study population), only Ocaliva-treated patients experienced a
reduction in liver stiffness below 16.9 kPa, a threshold associated
with the presence of cirrhosis. Mean liver stiffness reduction was
observed in the 10 mg Ocaliva group compared to placebo. In
patients with a baseline APRI score above 0.54 (a threshold
associated with increased risk of adverse clinical outcomes in PBC
patients), 35% of Ocaliva-treated patients compared to 13% of
placebo-treated patients experienced an improvement to below 0.54
at the end of the 12 month double-blind phase.
“Because liver biopsies are not routinely used for staging
patients with PBC, it is important that we explore non-invasive
strategies to evaluate the effects of new therapies like Ocaliva on
liver fibrosis,” said Gideon Hirschfield, M.D., Professor and
Honorary Consultant Hepatologist, Centre for Liver Research at the
University of Birmingham, UK, who presented the data. “These
results are very promising, and the ongoing Phase 4 COBALT trial of
Ocaliva will provide us with a more definitive understanding of the
drug’s ability to improve non-invasive measures of liver fibrosis
and reduce the risk of clinical outcomes in our patients with
PBC.”
The second POISE presentation (abstract #366) evaluated the
efficacy and safety of Ocaliva in the subset (17%) of patients with
cirrhosis who were at the greatest risk of progression to
liver-related adverse outcomes or death. At month 12, more
Ocaliva-treated patients with cirrhosis achieved the primary
composite study endpoint compared to placebo. Ocaliva treatment
improved markers of both cholestasis (alkaline phosphatase) and
hepatic impairment (bilirubin) relative to placebo in patients with
cirrhosis. Consistent with previous study results, pruritus (itch)
was the most common adverse event associated with Ocaliva
treatment. Additional side effects observed during the trial
included fatigue, abdominal pain and discomfort, rash,
oropharyngeal pain, dizziness, constipation, arthralgia, thyroid
function abnormality, and eczema.
“This exploratory analysis suggests that high-risk PBC patients
with compensated cirrhosis benefited from treatment with Ocaliva,
and the results were comparable to what we observed in earlier
stage non-cirrhotic patients,” said John Vierling, M.D., F.A.C.P.,
F.A.A.S.L.D., Professor of Medicine and Surgery at Baylor College
of Medicine, Past President of AASLD, and lead author of the
abstract. “The bilirubin improvements in these patients are
particularly meaningful because increasing bilirubin levels – even
within the normal range – are one of the hallmarks of progressive
disease and strongly associated with clinical outcomes.”
The third POISE presentation (abstract #401) examined the
effects of Ocaliva in PBC patients with mild and moderate renal
impairment. In this exploratory analysis, Ocaliva demonstrated
comparable efficacy regardless of renal status and enabled patients
with renal impairment to achieve significant improvements in
markers of cholestasis and hepatic damage. Ocaliva had no apparent
effect on renal safety, with mild to moderate pruritus the most
commonly occurring adverse event in all renal function groups.
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 Ocaliva® (obeticholic acid)Ocaliva
(obeticholic acid) is a potent and highly selective 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.
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.
In October 2016, the Committee for Medicinal Products for Human
Use (CHMP) of the European Medicines Agency (EMA) adopted a
positive opinion recommending the conditional marketing
authorization of Ocaliva in PBC. Based on the CHMP’s positive
recommendation, the final decision of the European Commission on
the conditional marketing authorization of Ocaliva in PBC is
expected by the end of 2016. 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.
To report SUSPECTED ADVERSE REACTIONS,
contact Intercept Pharmaceuticals, Inc. at 1-844-782-ICPT or FDA at
1-800-FDA-1088 or www.fda.gov/medwatch.
About the POISE TrialThe POISE trial studied
the safety and efficacy of once-daily treatment with Ocaliva in PBC
patients with an inadequate therapeutic response to, or who are
unable to tolerate, UDCA, the current standard of care. Of 216
patients randomized to three treatment arms—placebo, Ocaliva 5 mg
titrated to 10 mg or Ocaliva 10 mg—93% continued receiving UDCA.
The Ocaliva 5-10 mg titration group received Ocaliva 5 mg for six
months, after which dosing was increased to 10 mg based on
tolerability and biochemical response. The trial's primary endpoint
was a reduction in ALP to below a threshold of 1.67 times the upper
limit of normal, with a minimum of 15% reduction in ALP level from
baseline, and a normal bilirubin level after 12 months of
therapy.
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. 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, including Intercept’s
development program in NASH; 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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