Intercept Announces New Data to be Presented at the European Association for the Study of the Liver (EASL) Congress 2024
Phase 2Clinical ResultAccelerated ApprovalPhase 3
Intercept Announces New Data to be Presented at the European Association for the Study of the Liver (EASL) Congress 2024
Abstracts include late breaker featuring new six-month data from ongoing Phase 2 study evaluating the combination of obeticholic acid and bezafibrate in PBC
MORRISTOWN, N.J., May 29, 2024 (GLOBE NEWSWIRE) -- Intercept Pharmaceuticals, Inc., a biopharmaceutical company and wholly owned subsidiary of Alfasigma S.p.A. focused on the development and commercialization of novel therapeutics to treat rare and serious liver diseases, today announced nine abstracts related to primary biliary cholangitis (PBC) and alcohol-related liver disease will be presented at EASL Congress 2024. The congress will be held from June 5-8 in Milan, Italy.
“We are thrilled to present our latest research in PBC at this year’s EASL Congress,” said Sangeeta Sawhney, Senior Vice President and Head of U.S. Research & Development at Intercept. “The promising six-month results from one of our ongoing Phase 2 studies evaluating the combination of obeticholic acid and bezafibrate as well as new analyses from our landmark Phase 3 POISE trial underscore our commitment to advancing treatment options for people living with PBC. We look forward to sharing our findings with the global liver health community.”
Presentations by Intercept at EASL Congress 2024 include:
Late Breaker Poster Presentation
“Combined effect of obeticholic acid and bezafibrate in patients with primary biliary cholangitis and inadequate response or intolerance to ursodeoxycholic acid: 6-month results from a Phase 2 trial” (Abstract #LB136; Poster ID LBP-027)
Wednesday, June 5, 8:30 CEST
David Jones, Alexandre Louvet, Christophe Corpechot, Vaclav Hejda, Heng Zou, Antonio Civitarese, Alejandra Villamil, Frederick Nevens
PBC Poster Presentations
“Time to initiation of the second-line therapy obeticholic acid in patients with primary biliary cholangitis” (Abstract #1278; Poster ID THU-110)
Thursday, June 6, 8:30 CEST
Sonal Kumar, Joanna P. MacEwan, Alina Levine, Leona Bessonova, Radhika Nair, Darren Wheeler, Jing Li, Robert S. Brown, Jr.
“Obeticholic acid normalizes inflammatory biomarkers in patients with primary biliary cholangitis” (Abstract #3230; Poster ID THU-132)
Thursday, June 6, 8:30 CEST
David E. Jones, Christopher L. Bowlus, Arash Thranian, Mary Erickson, Jing Li, Christopher Gasink, Robert G. Gish
“Effect of obeticholic acid on reduction and normalization of alanine aminotransferase and aspartate aminotransferase in the Phase 3 POISE trial in primary biliary cholangitis” (Abstract #1322; Poster ID FRI-023)
Friday, June 7, 8:30 CEST
Robert G. Gish, Darren Wheeler, Jing Li, Christopher Gasink, David W. Victor III
“Evaluation of aspartate aminotransferase to platelet ratio index and fibrosis-4 index stabilization in the Phase 3 POISE trial of obeticholic acid for the treatment of primary biliary cholangitis” (Abstract #1315; Poster ID FRI-030)
Friday, June 7, 8:30 CEST
Alan Bonder, Darren Wheeler, Jing Li, Christopher Gasink, Robert G. Gish
“Stabilization of enhanced liver fibrosis and liver stiffness measures in the open-label extension of the Phase 3 POISE trial of obeticholic acid for the treatment of primary biliary cholangitis” (Abstract #1293; Poster ID FRI-015)
Friday, June 7, 8:30 CEST
Robert G. Gish, Darren Wheeler, Jing Li, Christopher Gasink, Alan Bonder
“Association of elevated liver biochemistries and clinical outcomes within strata of alkaline phosphatase levels in patients with primary biliary cholangitis” (Abstract #1301; Poster ID FRI-008)
Friday, June 7, 8:30 CEST
David W. Victor III, Joanna P. MacEwan, Jennifer Hernandez, Radhika Nair, Mustafa Kamal, Darren Wheeler, Jing Li, Leona Bessonova, Christopher Gasink, Kris V. Kowdley
Alcohol-related Liver Disease Poster Presentations
“Farnesoid X receptor agonistFarnesoid X receptor agonist INT-787 exhibits high intestinal localization” (Abstract #1313; Poster ID THU-316)
Thursday, June 6, 8:30 CEST
Jennifer Burkey, Sanjay Kansra, Antonio Macchiarulo, Kenneth Brouwer, Luciano Adorini, Mary Erickson, Roberto Pellicciari
“Farnesoid X receptor agonist INT-787 protects human liver organoids from alcohol-induced injury” (Abstract #1320; Poster ID TOP-313)
Thursday, June 6, 8:30 CEST
Francesca De Franco, Daniela Passeri, Sanjay Kansra, Luciano Adorini, Mary Erickson, Roberto Pellicciari
More information about these abstracts will be made available after the respective embargoes, as set by the EASL organizers, are lifted for each presentation. A full list of sessions at EASL Congress 2024 is available at www.easlcongress.eu.
About the Investigational OCA-bezafibrate Combination
Intercept has two ongoing Phase 2 studies (747-213 / NCT04594694, 747-214 / NCT05239468) that are exploring a range of therapeutic doses for the combination of OCA and bezafibrate for the potential treatment of individuals with PBC. OCA, a farnesoid X receptor (FXR) agonist, is marketed by Intercept as Ocaliva in the United States for the treatment of PBC (see below for full indication and Important Safety Information). Bezafibrate, a pan-peroxisome proliferator-activated receptor (pan-PPAR) agonist, is not approved in the United States for any indication.
FXR and PPAR are distinct pathways that each play a role in PBC. Simultaneously targeting both pathways may offer the greatest potential to impact bile acid synthesis, metabolism, and clearance that underly cholestatic liver diseases. Published studies establish a clinical proof-of-concept which suggests that the combination of OCA and bezafibrate may provide additive clinical efficacy and tolerability benefits in the treatment of PBC. OCA-bezafibrate combination therapy is investigational; safety and efficacy have not been established.
Primary 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 acid to build up in the liver, resulting in inflammation and scarring (fibrosis), which, if left untreated, can lead to cirrhosis, a liver transplant, or death.
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, 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 Resins
Bile 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.
Warfarin
CYP1A2 Substrates with Narrow Therapeutic Index
Obeticholic 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 Pump
Avoid 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.
About Intercept
Intercept is a biopharmaceutical company and a wholly owned subsidiary of Alfasigma S.p.A. focused on the development and commercialization of novel therapeutics to treat rare and serious liver diseases, including primary biliary cholangitis (PBC) and severe alcohol-associated hepatitis (sAH). Intercept owns the commercial rights to Ocaliva in the U.S. market. For more information, please visit www.interceptpharma.com or connect with the Company on LinkedIn, Threads and X (formerly Twitter).
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