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 a key publication in Gastroenterology showing that people
receiving OCA for primary biliary cholangitis (PBC) in a clinical
trial setting had greater transplant-free survival compared to
patients with PBC selected from “real-world” patient registries who
did not receive OCA.
Key findings include:
- Patients treated with OCA had an approximately 70 percent lower
relative risk of death or liver transplant than the control
patients at any time during follow-up.
- The primary outcome of time to first occurrence of liver
failure or death was statistically significant, favoring OCA
treatment in POISE compared to patients from “real-world”
databases.
- There was a statistically significant and clinically meaningful
reduction in death, liver transplant and hepatic decompensation in
OCA-treated patients versus comparable untreated patients.
“This important study is the first to demonstrate that
initiating treatment with OCA in appropriate patients with PBC
appears to have a meaningful impact on clinical outcomes,” said
Professor Gideon Hirschfield, FRCP, Ph.D., Lily and Terry Horner
Chair in Autoimmune Liver Disease at the University of Toronto. “I
am proud of this innovative analysis, and further, the continued
value we are deriving from large, academic-led, prospective
databases like the Global PBC and UK-PBC study groups. Leveraging
these registries helps advance our collective understanding of this
disease to ultimately influence clinical decision-making and
benefit people living with PBC.”
“Given the known challenges associated with conducting blinded,
placebo-controlled trials when the treatment has been approved and
is available, this study provides evidence that a well-matched
external comparator group can be a credible, alternate approach to
evaluating clinical efficacy,” said M. Michelle Berrey, M.D.,
M.P.H., President of Research & Development and Chief Medical
Officer of Intercept. “We look forward to further leveraging
real-world databases to continue generating insights on the
clinical benefit of Ocaliva in PBC.”
This study compared patients with PBC who received up to six
years of OCA in the Phase 3 POISE study and its open-label
extension (n=209) to external controls who were extracted from two
large, academic-led patient registries. External controls met POISE
entry criteria but were not treated with OCA. Treatment with
ursodeoxycholic acid (UDCA) was permitted.
The primary endpoint of this study was time to first occurrence
of liver transplant or death. Over the six-year follow-up, there
were five deaths/liver transplants in 209 subjects in the POISE
study, 135 in 1,381 patients in the Global PBC control, and 281 in
2,135 patients in the UK-PBC control. Preliminary results from this
analysis were first presented at the 2021 Annual Meeting of the
American Association for the Study of Liver Diseases (AASLD).
Data Sources for this Study: The Global PBC registry included
6,484 patients with PBC from eight countries in Europe and North
America during the study period who were not treated with OCA. Of
these, 1,381 met the entry criteria for this study.
The UK-PBC registry included over 6,900 patients with PBC from
the UK during the study period who were not treated with OCA. Of
these, 2,135 met the entry criteria for this study.
The POISE trial studied the safety and efficacy of once-daily
treatment with Ocaliva in PBC patients with an inadequate
therapeutic response to, or who were unable to tolerate,
ursodeoxycholic acid (UDCA). There were 217 patients randomized to
one of three groups in the trial: placebo, OCA 10 mg, or OCA 5 mg
for six months titrated to 10 mg based on clinical response. Seven
subjects did not participate in the open-label extension and were
not included in the current study. Patients completing the
double-blind phase had the option to continue in an open-label
extension (OLE) phase for a maximum of five additional years,
during which all patients received treatment with OCA 5-10 mg once
daily. Of the 198 patients who completed the double-blind phase,
more than 95 percent continued in the long-term safety extension
phase of the trial. Additional information regarding the POISE
trial can be found on the NIH clinical study listing website:
http://clinicaltrials.gov/ct2/show/NCT01473524.
About Primary Biliary CholangitisPrimary
biliary cholangitis (PBC) is a rare, progressive and chronic
autoimmune disease that affects the bile ducts in the liver and is
most prevalent (approximately 1 in 10,000) in women over the age of
40. PBC causes bile acids to build up in the liver, resulting in
inflammation and scarring (fibrosis), which, if left untreated, can
lead to cirrhosis, liver transplant, or death.
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). 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 intercurrent 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
StatementsThis press release contains forward-looking
statements (“FLS”), including regarding the results of our clinical
trials, and the safety and efficacy of OCA. Important factors could
cause actual results to differ materially from the FLS, including
further developments regarding understanding of side effects,
patient outcomes, or study methodology.
Contact
For more information about Intercept, please contact:
Investor inquiries: investors@interceptpharma.com
Media inquiries: media@interceptpharma.com
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