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
announced results from a new analysis examining obeticholic acid’s
(OCA) potential to improve transplant-free survival in patients
with PBC. The data will be featured in a late-breaking podium
presentation at The Liver Meeting®, the Annual Meeting of the
American Association for the Study of Liver Diseases (AASLD), which
is being held virtually from Friday, November 12 to Monday,
November 15, 2021. The analysis was also selected as a “Best of The
Liver Meeting” abstract in the Cholestatic and Autoimmune Liver
Diseases category.
“This collaborative study used an innovative approach to
contribute new understandings about how treatment of patients with
PBC with OCA may impact clinical outcomes: we compared patients
with PBC who were treated with OCA in the open-label long-term
safety extension of the Phase 3 POISE trial, with external controls
from two large representative academic-led patient registries. When
compared to real-world patient outcome data, the results provide
insights into OCA’s potential to improve transplant-free survival
in patients with PBC treated in a trial setting,” said Professor
Gideon Hirschfield, FRCP, Ph.D., Lily and Terry Horner Chair in
Autoimmune Liver Disease at the University of Toronto. “Data
describing the effect of OCA on mortality and need for liver
transplant in patients with PBC is eagerly awaited, but such data
is inevitably challenging to generate. Notably, when doing this
comparison, we found consistent results across the two databases.
We hope this analysis can soon be extended to include more patients
treated with OCA, and approaches such as this can help the field
overcome obstacles to generating meaningful clinical outcome
data.”
The POISE long-term safety extension (LTSE) study included 209
patients dosed with OCA with a maximum follow-up time of 6.3 years.
Propensity score-matched external controls were patients from the
Global PBC (n=1,391) and UK-PBC (n=2,138) real-world databases who
were diagnosed with PBC and who met POISE clinical trial entry
criteria. Patients from the external control databases were
untreated or treated with ursodeoxycholic acid (UDCA) with at least
one year of follow-up but were not treated with OCA or other
therapies. The primary endpoint was time to liver transplantation
or death.
In this analysis, 209 patients treated with OCA in the POISE
LTSE study had significantly greater transplant-free survival than
patients in the external control groups. In the OCA arm, three
events were observed versus 146 and 276 events in the Global PBC
and UK-PBC external control cohorts, respectively. In a weighted
analysis, the hazard ratio favoring OCA was 0.20 (0.06-0.64,
p=0.001) in Global PBC and 0.28 (0.09-0.90, p=0.033) in UK-PBC.
Thus, patients treated with OCA had a 72% to 80% lower risk of
death or liver transplant than the control groups at any time
during follow-up. Consistent findings were observed in multiple
sensitivity analyses, as well as when testing for the influence of
recruitment bias and potential confounding factors such as baseline
bilirubin, ALP, AST or ALT, age, PBC duration, UDCA use, diagnosis
year and sex.
“The methodology used in this study takes advantage of decades
of research to understand the natural history of PBC, and we are
thankful to all of the patients and researchers who have
contributed data to the Global PBC and UK-PBC study groups,” said
M. Michelle Berrey, M.D., M.P.H., President of Research &
Development and Chief Medical Officer of Intercept. “With a rare,
progressive disease like PBC, there are well-known difficulties in
conducting long-term, placebo-controlled trials after the approval
of a therapeutic agent, so studies like this provide another way to
address questions about the impact of OCA on clinical endpoints.
The results add to an already substantial body of evidence
supporting our belief in OCA’s potential to provide benefit for
appropriate patients with PBC. We are committed to generating
additional long-term data to build on these findings.”
About Primary Biliary CholangitisPrimary
biliary cholangitis (PBC) is a chronic, progressive liver disorder
that affects mostly women, impacting approximately one in 1,000
women over the age of 40. If left untreated, survival of patients
with PBC is significantly worse than the general population.
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) and nonalcoholic
steatohepatitis (NASH). Founded in 2002 in New York, Intercept
has operations in the United
States, Europe and Canada. For more information,
please visit www.interceptpharma.com or connect with the
company on Twitter and LinkedIn.
About Ocaliva® (obeticholic
acid)
OCALIVA, a farnesoid X receptor (FXR) agonist,
is indicated for the treatment of adult patients with primary
biliary cholangitis (PBC)
- without cirrhosis or
- with compensated cirrhosis who do not have evidence of portal
hypertension,
either in combination with ursodeoxycholic acid
(UDCA) with an inadequate response to UDCA or as monotherapy in
patients unable to tolerate UDCA.
This indication is approved under accelerated
approval based on a reduction in alkaline phosphatase (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.
IMPORTANT SAFETY INFORMATION
WARNING: HEPATIC DECOMPENSATION AND
FAILURE IN PRIMARY BILIARY CHOLANGITIS PATIENTS WITH
CIRRHOSIS
- Hepatic decompensation and
failure, sometimes fatal or resulting in liver transplant, have
been reported with OCALIVA treatment in primary biliary cholangitis
(PBC) patients with either compensated or decompensated
cirrhosis.
- OCALIVA is contraindicated
in PBC patients with decompensated cirrhosis, a prior
decompensation event, or with compensated cirrhosis who have
evidence of portal hypertension.
- Permanently discontinue
OCALIVA in patients who develop laboratory or clinical evidence of
hepatic decompensation; have compensated cirrhosis and develop
evidence of portal hypertension, or experience clinically
significant hepatic adverse reactions while on
treatment.
Contraindications
OCALIVA is contraindicated in patients with:
- decompensated cirrhosis (e.g., Child-Pugh Class B or C) or a
prior decompensation event
- compensated cirrhosis who have evidence of portal hypertension
(e.g., ascites, gastroesophageal varices, persistent
thrombocytopenia)
- complete biliary obstruction
Warnings and Precautions
Hepatic Decompensation and Failure in PBC Patients with
Cirrhosis
Hepatic decompensation and failure, sometimes
fatal or resulting in liver transplant, have been reported with
OCALIVA treatment in PBC patients with cirrhosis, either
compensated or decompensated. Among post-marketing cases reporting
it, median time to hepatic decompensation (e.g., new onset ascites)
was 4 months for patients with compensated cirrhosis; median time
to a new decompensation event (e.g., hepatic encephalopathy) was
2.5 months for patients with decompensated cirrhosis.
Some of these cases occurred in patients with
decompensated cirrhosis when they were treated with higher than the
recommended dosage for that patient population; however, cases of
hepatic decompensation and failure have continued to be reported in
patients with decompensated cirrhosis even when they received the
recommended dosage.
Hepatotoxicity was observed in the OCALIVA
clinical trials. A dose-response relationship was observed for the
occurrence of hepatic adverse reactions including jaundice,
worsening 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 two 3-month,
placebo-controlled clinical trials in patients with primarily early
stage PBC.
Routinely monitor patients for progression of
PBC, including hepatic adverse reactions, with laboratory and
clinical assessments to determine whether drug discontinuation is
needed. Closely monitor patients with compensated cirrhosis,
concomitant hepatic disease (e.g., autoimmune hepatitis, alcoholic
liver disease), and/or with severe intercurrent illness for new
evidence of portal hypertension (e.g., ascites, gastroesophageal
varices, persistent thrombocytopenia), or increases above the upper
limit of normal in total bilirubin, direct bilirubin, or
prothrombin time to determine whether drug discontinuation is
needed. Permanently discontinue OCALIVA in patients who develop
laboratory or clinical evidence of hepatic decompensation (e.g.,
ascites, jaundice, variceal bleeding, hepatic encephalopathy), have
compensated cirrhosis and develop evidence of portal hypertension
(e.g., ascites, gastroesophageal varices, persistent
thrombocytopenia), experience clinically significant hepatic
adverse reactions, or develop complete biliary obstruction. If
severe incurrent illness occurs, interrupt treatment with OCALIVA
and monitor the patient’s liver function. After resolution of the
intercurrent illness, consider the potential risks and benefits of
restarting OCALIVA treatment.
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 a 12-month
double-blind randomized controlled clinical 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. Consider clinical evaluation of
patients with new onset or worsening severe pruritus. Management
strategies include the addition of bile acid binding 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). 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. Monitor
patients for changes in serum lipid levels during treatment. For
patients who do not respond to OCALIVA after 1 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 (≥5%) are:
pruritus, fatigue, abdominal pain and discomfort, rash,
oropharyngeal pain, dizziness, constipation, arthralgia, thyroid
function abnormality, and eczema.
Drug Interactions
- Bile Acid Binding ResinsBile acid binding resins such as
cholestyramine, colestipol, or colesevelam adsorb and reduce bile
acid absorption and may reduce the absorption, systemic exposure,
and efficacy of OCALIVA. If taking a bile acid binding resin, take
OCALIVA at least 4 hours before or 4 hours after taking the bile
acid binding resin, or at as great an interval as possible.
- WarfarinThe International Normalized Ratio (INR) decreased
following coadministration of warfarin and OCALIVA. Monitor INR and
adjust the dose of warfarin, as needed, to maintain the target INR
range when co-administering OCALIVA and warfarin.
- CYP1A2 Substrates with Narrow Therapeutic IndexObeticholic acid
may increase the exposure to concomitant drugs that are CYP1A2
substrates. Therapeutic monitoring of CYP1A2 substrates with a
narrow therapeutic index (e.g., theophylline and tizanidine) is
recommended when co-administered with OCALIVA.
- Inhibitors of Bile Salt Efflux PumpAvoid concomitant use of
inhibitors of the bile salt efflux pump (BSEP) such as
cyclosporine. Concomitant medications that inhibit canalicular
membrane bile acid transporters such as the BSEP may exacerbate
accumulation of conjugated bile salts including taurine conjugate
of obeticholic acid in the liver and result in clinical symptoms.
If concomitant use is deemed necessary, monitor serum transaminases
and bilirubin.
Please click here for
Full Prescribing Information, including
Boxed WARNING.
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.
Cautionary Note Regarding Forward-Looking
Statements This press release contains forward-looking
statements, including, but not limited to, statements regarding the
progress, timing and results of our clinical trials, including our
clinical trials for the treatment of nonalcoholic steatohepatitis
(“NASH”), the safety and efficacy of our approved product, Ocaliva
(obeticholic acid or “OCA”) for primary biliary cholangitis
(“PBC”), and our product candidates, including OCA for liver
fibrosis due to NASH, the timing and acceptance of our regulatory
filings and the potential approval of OCA for liver fibrosis due to
NASH, the review of our New Drug Application for OCA for the
treatment of liver fibrosis due to NASH by the U.S. Food and Drug
Administration (FDA), our intent to work with the FDA to address
the issues raised in the complete response letter (CRL), the
potential commercial success of OCA, as well as our strategy,
future operations, future financial position, future revenue,
projected costs, financial guidance, prospects, plans and
objectives.
These statements constitute forward-looking statements within
the meaning of Section 27A of the Securities Act of 1933, as
amended, and Section 21E of the Securities Exchange Act of 1934, as
amended. The words “anticipate,” “believe,” “estimate,” “expect,”
“intend,” “may,” “plan,” “predict,” “project,” “target,”
“potential,” “will,” “would,” “could,” “should,” “possible,”
“continue” and similar expressions are intended to identify
forward-looking statements, although not all forward-looking
statements contain these identifying words. Readers are cautioned
not to place undue reliance on these forward-looking statements,
which speak only as of the date of this release, and we undertake
no obligation to update any forward-looking statement except as
required by law. These forward-looking statements are based on
estimates and assumptions by our management that, although believed
to be reasonable, are inherently uncertain and subject to a number
of risks. The following represent some, but not necessarily all, of
the factors that could cause actual results to differ materially
from historical results or those anticipated or predicted by our
forward-looking statements: our ability to successfully
commercialize Ocaliva for PBC; our ability to maintain our
regulatory approval of Ocaliva for PBC in the United States,
Europe, Canada, Israel, Australia and other jurisdictions in which
we have or may receive marketing authorization; our ability to
timely and cost-effectively file for and obtain regulatory approval
of our product candidates on an accelerated basis or at all,
including OCA for liver fibrosis due to NASH following the issuance
of the CRL by the FDA; any advisory committee recommendation or
dispute resolution determination that our product candidates,
including OCA for liver fibrosis due to NASH, should not be
approved or approved only under certain conditions; any future
determination that the regulatory applications and subsequent
information we submit for our product candidates, including OCA for
liver fibrosis due to NASH, do not contain adequate clinical or
other data or meet applicable regulatory requirements for approval;
conditions that may be imposed by regulatory authorities on our
marketing approvals for our products and product candidates,
including OCA for liver fibrosis due to NASH, such as the need for
clinical outcomes data (and not just results based on achievement
of a surrogate endpoint), any risk mitigation programs such as a
REMS, and any related restrictions, limitations and/or warnings
contained in the label of any of our products or product
candidates; any potential side effects associated with Ocaliva for
PBC, OCA for liver fibrosis due to NASH or our other product
candidates that could delay or prevent approval, require that an
approved product be taken off the market, require the inclusion of
safety warnings or precautions, or otherwise limit the sale of such
product or product candidate, including in connection with our
update to Ocaliva prescribing information in May 2021
contraindicating Ocaliva for patients with PBC and decompensated
cirrhosis, a prior decompensation event, or compensated cirrhosis
with evidence of portal hypertension; the initiation, timing, cost,
conduct, progress and results of our research and development
activities, preclinical studies and clinical trials, including any
issues, delays or failures in identifying patients, enrolling
patients, treating patients, retaining patients, meeting specific
endpoints in the jurisdictions in which we intend to seek approval
or completing and timely reporting the results of our NASH or PBC
clinical trials; the outcomes of interactions with regulators
(e.g., the FDA and the European Medicines Agency) regarding our
clinical trials; our ability to establish and maintain
relationships with, and the performance of, third-party
manufacturers, contract research organizations and other vendors
upon whom we are substantially dependent for, among other things,
the manufacture and supply of our products, including Ocaliva for
PBC and, if approved, OCA for liver fibrosis due to NASH, and our
clinical trial activities; our ability to identify, develop and
successfully commercialize our products and product candidates,
including our ability to successfully launch OCA for liver fibrosis
due to NASH, if approved; our ability to obtain and maintain
intellectual property protection for our products and product
candidates, including our ability to cost-effectively file,
prosecute, defend and enforce any patent claims or other
intellectual property rights; the size and growth of the markets
for our products and product candidates and our ability to serve
those markets; the degree of market acceptance of Ocaliva for PBC
and, if approved, OCA for liver fibrosis due to NASH or our other
product candidates among physicians, patients and healthcare
payors; the availability of adequate coverage and reimbursement
from governmental and private healthcare payors for our products,
including Ocaliva for PBC and, if approved, OCA for liver fibrosis
due to NASH, and our ability to obtain adequate pricing for such
products; our ability to establish and maintain effective sales,
marketing and distribution capabilities, either directly or through
collaborations with third parties; competition from existing drugs
or new drugs that become available; our ability to attract and
retain key personnel to manage our business effectively; our
ability to prevent or defend against system failures or security or
data breaches due to cyber-attacks, or cyber intrusions, including
ransomware, phishing attacks and other malicious intrusions; our
ability to comply with data protection laws; costs and outcomes
relating to any disputes, governmental inquiries or investigations,
regulatory proceedings, legal proceedings or litigation, including
any securities, intellectual property, employment, product
liability or other litigation; our collaborators’ election to
pursue research, development and commercialization activities; our
ability to establish and maintain relationships with collaborators
with development, regulatory and commercialization expertise; our
need for and ability to generate or obtain additional financing;
our estimates regarding future expenses, revenues and capital
requirements and the accuracy thereof; our use of cash, cash
equivalents and short-term investments; our ability to acquire,
license and invest in businesses, technologies, product candidates
and products; our ability to manage the growth of our operations,
infrastructure, personnel, systems and controls; our ability to
obtain and maintain adequate insurance coverage; continuing threats
from COVID-19, including additional waves of infections, and their
impacts including quarantines and other government actions, delays
relating to our regulatory applications, disruptions relating to
our ongoing clinical trials or involving our contract research
organizations, study sites or other clinical partners, disruptions
relating to our supply chain or involving our third-party
manufacturers, distributors or other distribution partners, and
facility closures or other restrictions, and impact of the
foregoing on our results of operations and financial position; the
impact of general U.S. and foreign economic, industry, market,
regulatory or political conditions, including the impact of Brexit;
and the other risks and uncertainties identified in our periodic
filings filed with the U.S. Securities and Exchange Commission,
including our Annual Report on Form 10-K for the year ended
December 31, 2020.
CONTACT
For more information about Intercept, please contact:
For investors:investors@interceptpharma.com
For media:media@interceptpharma.com
Source: Intercept Pharmaceuticals, Inc.
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