Cholestyramine

Abstracts include a presidential plenary-selected Phase 2 study evaluating the combination of obeticholic acid and bezafibrate in PBC, along with 10 other abstractsMORRISTOWN, N.J., April 30, 2025 (GLOBE NEWSWIRE) -- Intercept Pharmaceuticals, Inc. (Intercept), part of the Alfasigma Group, today announced 11 submitted abstracts have been accepted for presentation at Digestive Disease Week 2025, including oral presentations of data from a Phase 2 study evaluating the combination of obeticholic acid and bezafibrate in PBC, and investigational data for INT-787, a next-generation FXR agonist. The conference will be held from May 3-6 in San Diego. The abstracts showcase the Company’s breadth of research in the gastrointestinal (GI) and hepatology therapeutic areas. The data encompass multiple areas of high unmet need, including primary biliary cholangitis (PBC); primary sclerosing cholangitis (PSC); severe alcohol-associated hepatitis (sAH), a liver disease increasing in prevalence, especially among women; and chronic intestinal pseudo-obstruction (CIPO), a rare condition characterized by severe impairment of intestinal activity. “We look forward to sharing details of our clinical-development program progress with the scientific community, including our ongoing Phase 2 study of a potential first-in-class treatment for severe alcohol-associated hepatitis,” said Sangeeta Sawhney, M.D., Senior Vice President, Global Head, GI Therapeutic Area, Alfasigma. “We're also going to share the first six-year data for a second-line therapy for PBC, which gives insights into long-term safety and effectiveness." Presentations by Intercept and Alfasigma at DDW 2025: Oral Presentations “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” (Presentation #4)Session: AASLD Presidential PlenarySaturday, May 3, 9:15 AM ETChristophe Corpechot, Vaclav Hejda, Heng Zou, Antonio Civitarese, Alejandra Villamil, Frederik Nevens “FXR AGONIST INT-787 INHIBITS INFLAMMATION, FIBROSIS, SENESCENCE, AND APOPTOSIS ARREST IN HUMAN CHOLANGIOCYTES MODELING PSC” (Presentation #879)Session: Cutting-Edge Insights into PSC: From Mechanisms to TherapiesMonday, May 5, 4:45 PM ETFrancesca De Franco, Daniela Passeri, Sanjay Kansra, Luciano Adorini, Mary Erickson, Roberto Pellicciari Poster Presentations “OBETICHOLIC ACID NORMALIZES INFLAMMATORY BIOMARKERS IN PATIENTS WITH PRIMARY BILIARY CHOLANGITIS” (Poster #Sa1500)Session: Liver Inflammation and ImmunobiologySaturday, May 3, 12:30 PM ETDavid E. Jones, Christopher L. Bowlus, Arash Thranian, Mary Erickson, Jing Li, Christopher Gasink, Robert G. Gish “US POPULATION–BASED EPIDEMIOLOGY OF PRIMARY BILIARY CHOLANGITIS: EXAMINATION OF PATIENT CHARACTERISTICS AND INCIDENCE OF HEPATIC OUTCOMES IN A US HEALTHCARE CLAIMS DATABASE” (Poster #Su1675)Session: Health Disparities in Patients with Liver DiseaseSunday, May 4, 12:30 PM ETAparna Goel, Bridget L. Balkaran, Chris White, Radhika Nair, Anne Chiplin, Jing Li, Jayashri Desai, Joanna P. MacEwan “REAL-WORLD ADHERENCE TO OBETICHOLIC ACID THERAPY FOR PRIMARY BILIARY CHOLANGITIS” (Poster #Mo1626)Session: Human and Experimental Cholestatic and Autoimmune Liver DiseasesMonday, May 5, 12:30 PM ETRobert G. Gish, Joanna P. MacEwan, Jennifer Hernandez, Radhika Nair, Jing Li, Darren Wheeler, Anh Singhania, Leona Bessonova “PATIENTS WITHOUT BASELINE PRURITUS WHO INITIATE TREATMENT WITH OCA HAVE SIMILAR RISK OF DEVELOPING TREATMENT-EMERGENT PRURITUS AS THOSE WHO ARE NOT ON TREATMENT WITH OCA” (Poster #Mo1618)Session: Human and Experimental Cholestatic and Autoimmune Liver DiseasesMonday, May 5, 12:30 PM ETDavid Jones, Aparna Goel, Ann Moore, Jing Li, Darren Wheeler, Christopher White, and David W. Victor III “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” (Poster #Mo1667)Session: Non-Invasive Assessment of Liver DiseaseMonday, May 5, 12:30 PM ET Robert G. Gish, Darren Wheeler, Jing Li, Christopher Gasink, Alan Bonder “FARNESOID X RECEPTOR AGONIST INT-787 PROTECTS HUMAN LIVER ORGANOIDS FROM ALCOHOL-INDUCED INJURY” (Poster #Su1618)Session: Alcoholic-associated Liver Disease Including Alcohol-associated HepatitisSunday, May 4, 12:30 PM ETFrancesca De Franco, Daniela Passeri, Sanjay Kansra, Luciano Adorini, Mary Erickson, Roberto Pellicciari “FARNESOID X RECEPTOR AGONIST INT-787 EXHIBITS HIGH INTESTINAL LOCALIZATION” (Poster #Su1635)Session: Alcoholic-associated Liver Disease Including Alcohol-associated HepatitisSunday, May 4, 12:30 PM ETJennifer Burkey, Sanjay Kansra, Antonio Macchiarulo, Kenneth Brouwer, Luciano Adorini, Mary Erickson, Roberto Pellicciari “PHARMACOKINETIC AND PHARMACODYNAMIC INTERACTION OF OBETICHOLIC ACID AND BEZAFIBRATE IN HEALTHY VOLUNTEERS” (Poster #Mo1628)Session: Human and Experimental Cholestatic and Autoimmune Liver DiseasesMonday, May 5, 12:30 PM ETJennifer Burkey, Karen Brown, Heng Zou, Jennifer Boston, Mary Erickson “DEVELOPMENT OF A DE NOVO CLINICAL OUTCOME ASSESSMENT FOR CHRONIC INTESTINAL PSEUDO-OBSTRUCTION" (Poster #Mo1258)Session: Patient Report and Clinical Outcomes: IBD, GERC, Functional Disorders, Other Monday, May 5, 12:30 PM ETMadhusudan Grover, Jan Tack, Sara Manzoni, Elena Pasquali, Valeria Scuderi, Vincenzo Stanghellini More information about these presentations will be made available after the respective embargoes, as set by the DDW organizers, are lifted for each presentation. A full list of sessions at DDW 2025 is available at www.ddw.org. Attendees of DDW can visit Intercept at booths #2011 and #2411 throughout the meeting. About Digestive Disease WeekDigestive Disease Week (DDW) is the largest international gathering of physicians, researchers and academics in the fields of gastroenterology, hepatology, endoscopy and gastrointestinal surgery. Jointly sponsored by the American Association for the Study of Liver Diseases (AASLD), the American Gastroenterological Association (AGA), the American Society for Gastrointestinal Endoscopy (ASGE) and the Society for Surgery of the Alimentary Tract (SSAT), DDW is an in-person and online meeting from May 3-6, 2025. The meeting showcases more than 5,600 abstracts and hundreds of lectures on the latest advances in GI research, medicine and technology. More information can be found at www.ddw.org. 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 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 Severe Alcohol-Associated Hepatitis (sAH)Alcohol-related liver disease (ALD) as a cause of chronic liver disease is on the rise in the U.S. and is currently the leading indication for liver transplant listing overall in the U.S. Patients with severe alcohol-associated hepatitis (sAH) are now younger, with an increased representation of females compared to past decades, reflecting changing patterns of alcohol consumption in the U.S. Currently, there are no medicines with an approved indication to treat patients with sAH. About Primary Sclerosing CholangitisPrimary sclerosing cholangitis (PSC) is a rare, life-threatening, chronic cholestatic liver disease characterized by progressive destruction of bile ducts that leads to the development of cirrhosis and end-stage liver disease or cancer in a majority of patients. About the Investigational Obeticholic Acid-Bezafibrate CombinationIntercept has two ongoing Phase 2 studies (747-213 / NCT04594694, 747-214 / NCT05239468) that are exploring a range of therapeutic doses for the combination of obeticholic acid (OCA) and bezafibrate for the potential treatment of individuals with PBC. Obeticholic acid, 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 obeticholic acid and bezafibrate may provide additive clinical efficacy and tolerability benefits in the treatment of PBC. Obeticholic acid-bezafibrate combination therapy is investigational; safety and efficacy have not been established. 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 orwith 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 eventcompensated 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 four 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 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 (≥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 four hours before or four hours after taking the bile acid binding resin, or at as great an interval as possible.Warfarin The 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 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 InterceptIntercept, part of the Alfasigma Group since 2023, focuses on the development and commercialization of novel therapeutics to treat serious liver and GI 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, and X (formerly Twitter). About Alfasigma Alfasigma is a global pharmaceutical company founded over 75 years ago in Italy, where it is headquartered (in Bologna and Milan). The Group operates in over 100 markets spanning Europe, North and South America, Asia, and Africa. It has offices in many countries, including Italy, the United States (US), Spain, Germany, Mexico, and China; production sites in Italy, Spain, and the US; and R&D labs in Italy (Pomezia and Bergamo). Alfasigma employs approximately 4,000 people dedicated to research, development, production, and distribution of medicinal products contributing to its mission to provide better health and a better quality of life for patients, caregivers, and healthcare providers. It focuses on three main therapeutic areas: Gastroenterology/Hepatology, Vascular, and Rheumatology. Its portfolio spans from primary care to specialty care, rare disease medications, and consumer health products, including medical foods and nutraceuticals. For more information, please visit www.alfasigma.com or connect with the Company on LinkedIn, ContactFor more information about Intercept, please contact: media@interceptpharma.com

MORRISTOWN, N.J., Nov. 12, 2024 (GLOBE NEWSWIRE) -- Intercept Pharmaceuticals, Inc., a wholly owned biopharmaceutical subsidiary of Alfasigma S.p.A., today announced that the U.S. Food and Drug Administration (FDA) has issued a Complete Response Letter (CRL) that addresses the supplemental New Drug Application (sNDA) for OCALIVA® (obeticholic acid, OCA) seeking full approval for the treatment of indicated patients with primary biliary cholangitis (PBC) – a rare, progressive disease that disproportionally affects women. The FDA informed Intercept that it is unable to approve the sNDA in its current form, consistent with the outcome of the Gastrointestinal Drugs Advisory Committee (GIDAC) meeting in September 2024. In its letter, the FDA also said it was continuing to consider safety data from Study 747-302, along with other safety information. OCALIVA continues to be available for the treatment of appropriate patients living with PBC in the U.S. under accelerated approval status. Healthcare professionals who have questions about OCALIVA can contact Intercept Medical Information, and patients with questions should contact their healthcare providers. “We believe in the totality of evidence supporting OCALIVA and intend to work closely with the FDA on next steps,” said Vivek Devaraj, U.S. President and Chairman at Intercept. “We remain committed to patients living with PBC who have limited treatment options.” OCALIVA’s safety profile is based on extensive data from long-term clinical-trials, published real-world evidence and external-control studies, as well as 8 years of post-marketing patient experience that collectively spans 42,000 patient years. 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 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 InterceptIntercept 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). 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 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 The 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 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. ContactFor more information about Intercept, please contact:For media:media@interceptpharma.com