Bezalip SR (bezafibrate) / AbbVie, Intercept, Miravo - LARVOL DELTA

Study of OCA in Combination With BZF Evaluating Efficacy, Safety, and Tolerability in Participants With PBC (clinicaltrials.gov) - P2 | N=75 | Terminated | Sponsor: Intercept Pharmaceuticals | Active, not recruiting ➔ Terminated; Intercept made a business decision to terminate the study based on FDA's request for voluntary withdrawal of Ocaliva and the issuance of clinical hold on studies under US IND involving OCA.

Trial termination • Hepatology • Immunology • Primary Biliary Cholangitis

To Evaluate Safety and Tolerability of the Fixed- Dose Combination of Obeticholic Acid and Bezafibrate (clinicaltrials.gov) - P3 | N=63 | Terminated | Sponsor: Intercept Pharmaceuticals | N=133 ➔ 63 | Active, not recruiting ➔ Terminated; Intercept made a business decision to terminate the study based on FDA's request for voluntary withdrawal of Ocaliva and the issuance of clinical hold on studies under US IND involving OCA.

Enrollment change • Trial termination • Hepatology • Immunology • Primary Biliary Cholangitis

LONG-TERM SAFETY OF COMBINATION OBETICHOLIC ACID AND BEZAFIBRATE IN PATIENTS WITH PRIMARY BILIARY CHOLANGITIS: INTERIM DATA FROM TWO PHASE 2 TRIALS (AASLD 2025) - P2 | "Here, we present long-term safety data from 2 phase 2 trials evaluating OCA and BZF combination therapy in patients (pts) with PBC who had inadequate response or intolerance to ursodeoxycholic acid... OCA + BZF combination therapy was generally well tolerated across both studies, with no deaths or liver transplants and few serious AEs. The safety profile supports continued phase 3 development of fixed-dose combination therapy for pts with PBC."

Clinical • P2 data • Hepatology • Immunology • Liver Failure • Primary Biliary Cholangitis • Renal Disease

ANTICHOLESTATIC EFFECTS OF OBETICHOLIC ACID AND BEZAFIBRATE IN COMBINATION COMPARED WITH ELAFIBRANOR AND SELADELPAR IN A HUMAN HEPATOCYTE MODEL OF CHOLESTASIS (AASLD 2025) - "The combination of OCA + BZF was more efficacious than either drug alone or the recently approved PPAR agonists, ELA and SEL, in regulating genes involved in cholestasis, resulting in enhanced suppression of bile acid synthesis, increased bile acid secretion, and increased bilirubin metabolism."

Cholestasis • Hepatology • Immunology • Liver Failure • Primary Biliary Cholangitis • FGF19 • UGT1A1

Study of OCA in Combination With BZF Evaluating Efficacy, Safety and Tolerability in Participants With PBC (clinicaltrials.gov) - P2 | N=72 | Completed | Sponsor: Intercept Pharmaceuticals | Active, not recruiting ➔ Completed

Trial completion • Hepatology • Immunology • Primary Biliary Cholangitis

To Evaluate Safety and Tolerability of the Fixed- Dose Combination of Obeticholic Acid and Bezafibrate (clinicaltrials.gov) - P3 | N=133 | Active, not recruiting | Sponsor: Intercept Pharmaceuticals | Enrolling by invitation ➔ Active, not recruiting | Trial completion date: Mar 2030 ➔ Oct 2025 | Trial primary completion date: Jan 2029 ➔ Oct 2025

Enrollment closed • Trial completion date • Trial primary completion date • Hepatology • Immunology • Primary Biliary Cholangitis

PHARMACOKINETIC AND PHARMACODYNAMIC INTERACTION OF OBETICHOLIC ACID AND BEZAFIBRATE IN HEALTHY VOLUNTEERS (DDW 2025) - "Background: Obeticholic acid (OCA), a selective farnesoid X receptor agonist, received accelerated approval for treating adults with primary biliary cholangitis (PBC) with an inadequate response to ursodeoxycholic acid (UDCA)... BZF increased total OCA plasma levels with high variability, while OCA had a slight effect on BZF levels. Together, they reduced C4 to a larger extent than either alone, suggesting a potential incremental benefit of their combination on reducing BA synthesis compared with OCA alone."

Clinical • PK/PD data • Hepatology • Immunology • Primary Biliary Cholangitis • FGF19

Intercept Announces Data to be Presented at Digestive Disease Week 2025 (GlobeNewswire) - "Intercept Pharmaceuticals...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."

Clinical data • Hepatology • Primary Biliary Cholangitis

Study of OCA in Combination With BZF Evaluating Efficacy, Safety and Tolerability in Participants With PBC (clinicaltrials.gov) - P2 | N=60 | Active, not recruiting | Sponsor: Intercept Pharmaceuticals | Trial completion date: Feb 2025 ➔ Oct 2025 | Trial primary completion date: Nov 2024 ➔ Oct 2025

Trial completion date • Trial primary completion date • Hepatology • Immunology • Primary Biliary Cholangitis

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 (ACG 2024) - "The DB tx period included 75 pts; 66 pts continued to the LTSE. OCA/B400 SR demonstrated a 65.3% reduction in ALP and 27.6% reduction in TB; 61.1% of pts in this cohort achieved ALP ≤ ULN and 83.3% achieved TB ≤ 0.6 x ULN ( Figure 1 ). OCA/B400 SR induced biochemical remission in 66.7% of pts and induced the greatest change in GLOBE (–0.7) and UK-PBC (–1.1) scores."

Clinical • P2 data • Dermatology • Dyslipidemia • Hepatology • Immunology • Primary Biliary Cholangitis • Pruritus

PHARMACOKINETIC AND PHARMACODYNAMIC INTERACTION OF OBETICHOLIC ACID AND BEZAFIBRATE IN HEALTHY VOLUNTEERS (AASLD 2024) - "Background: Obeticholic acid (OCA), a selective farnesoid X receptor agonist, received accelerated approval for treating adults with primary biliary cholangitis (PBC) with an inadequate response to ursodeoxycholic acid (UDCA)... BZF increased total OCA plasma levels with high variability, while OCA had a slight effect on BZF levels. Together, they reduced C4 to a larger extent than either alone at a low dose of OCA, suggesting potential incremental benefit of their combination on reducing BA synthesis compared with OCA alone."

Clinical • PK/PD data • Hepatology • Immunology • Primary Biliary Cholangitis • FGF19

To Evaluate Safety and Tolerability of the Fixed- Dose Combination of Obeticholic Acid and Bezafibrate (clinicaltrials.gov) - P3 | N=133 | Enrolling by invitation | Sponsor: Intercept Pharmaceuticals | Not yet recruiting ➔ Enrolling by invitation | Trial primary completion date: Jan 2025 ➔ Jan 2029

Enrollment open • Trial primary completion date • Hepatology • Immunology • Primary Biliary Cholangitis

To Evaluate Safety and Tolerability of the Fixed- Dose Combination of Obeticholic Acid and Bezafibrate (clinicaltrials.gov) - P3 | N=133 | Not yet recruiting | Sponsor: Intercept Pharmaceuticals

New P3 trial • Hepatology • Immunology • Primary Biliary Cholangitis

Study of OCA in Combination With BZF Evaluating Efficacy, Safety and Tolerability in Participants With PBC (clinicaltrials.gov) - P2 | N=60 | Active, not recruiting | Sponsor: Intercept Pharmaceuticals | Trial completion date: Aug 2024 ➔ Feb 2025 | Trial primary completion date: Aug 2024 ➔ Nov 2024

Combination therapy • Trial completion date • Trial primary completion date • Hepatology • Immunology • Primary Biliary Cholangitis

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 (EASL-ILC 2024) - "These results suggest that OCA + BZF is generally well tolerated and has therapeutic potential to normalize multiple serum biomarkers associated with improved transplant-free and decompensation-free survival. Low rates of pruritus were observed with OCA/B400 SR, which were substantially lower than those with OCA in the phase 3 POISE study (56%-68%). The data support phase 3 development of the SR formulation of BZF with low doses of OCA."

Clinical • Late-breaking abstract • P2 data • Dermatology • Dyslipidemia • Hepatology • Immunology • Primary Biliary Cholangitis • Pruritus

METABOLIC OUTCOMES AND KEY EFFICACY DATA FROM A PHASE 2 TRIAL EVALUATING COMBINATION OBETICHOLIC ACID AND BEZAFIBRATE IN PATIENTS WITH PRIMARY BILIARY CHOLANGITIS (DDW 2024) - "Introduction : Obeticholic acid (OCA), a potent farnesoid X receptor agonist, is indicated as a second-line treatment for patients (pts) with primary biliary cholangitis (PBC) who have an inadequate response or intolerance to ursodeoxycholic acid...Conclusions : The short-term administration of OCA and BZF has therapeutic potential to normalize multiple key serum biomarkers of PBC-related liver damage that have been correlated with improved transplant-free and decompensation-free survival. Combination OCA and BZF therapy has an acceptable metabolic profile, which includes a positive impact on total cholesterol and LDL-C."

Clinical • P2 data • Dyslipidemia • Hepatology • Immunology • Primary Biliary Cholangitis • Transplantation

Study of OCA in Combination With BZF Evaluating Efficacy, Safety, and Tolerability in Participants With PBC (clinicaltrials.gov) - P2 | N=72 | Active, not recruiting | Sponsor: Intercept Pharmaceuticals | Trial completion date: Dec 2024 ➔ Dec 2025 | Trial primary completion date: Oct 2024 ➔ Oct 2025

Combination therapy • Trial completion date • Trial primary completion date • Hepatology • Immunology • Primary Biliary Cholangitis

Study of OCA in Combination With BZF Evaluating Efficacy, Safety and Tolerability in Participants With PBC (clinicaltrials.gov) - P2 | N=60 | Active, not recruiting | Sponsor: Intercept Pharmaceuticals | Phase classification: P2a ➔ P2

Combination therapy • Phase classification • Hepatology • Immunology • Primary Biliary Cholangitis

Phase 2 Studies Show OCA-Bezafibrate Achieves Biochemical Remission, ALP Reduction (HCPLive) - "'Results from these studies illustrate the OCA-bezafibrate combination's potential to deliver biochemical responses across a range of biomarkers that predict improved clinical outcomes in PBC,' said Cynthia Levy, MD...'These positive findings, including low rates of pruritus, are an important milestone for the PBC community.'"

Media quote

Q&A: Combination OCA-Bezafibrate for PBC, with Cynthia Levy, MD (HCPLive) - "Levy: The two Phase 2 studies remain ongoing and are continuing to explore a range of therapeutic doses and formulations for the combination of OCA and bezafibrate. Looking ahead, the results presented at The Liver Meeting support progression to Phase 3 trials with sustained release formulation of bezafibrate and low doses of OCA....We are looking forward to confirming the synergistic effect of this potent drug combination, as each of them has been suggested to improve survival free of liver transplantation based on real world data."

Media quote

Intercept Announces New Phase 2 Data Showing Significant Impact of OCA-Bezafibrate Combination on Normalization of Multiple Key Biomarkers of PBC-Induced Liver Damage at AASLD The Liver Meeting 2023 (BioSpace) - '"Results from these studies illustrate the OCA-bezafibrate combination's potential to deliver biochemical responses across a range of biomarkers that predict improved clinical outcomes in PBC,' said Cynthia Levy, M.D., Hepatologist at the University of Miami Hospital and Professor of Medicine at the University of Miami. 'These positive findings, including low rates of pruritus, are an important milestone for the PBC community.'"

Biomarker • P2 data

Study of OCA in Combination With BZF Evaluating Efficacy, Safety, and Tolerability in Participants With PBC (clinicaltrials.gov) - P2 | N=72 | Active, not recruiting | Sponsor: Intercept Pharmaceuticals | Recruiting ➔ Active, not recruiting

Combination therapy • Enrollment closed • Hepatology • Immunology • Primary Biliary Cholangitis

Study of OCA in Combination With BZF Evaluating Efficacy, Safety and Tolerability in Participants With PBC (clinicaltrials.gov) - P2a | N=60 | Active, not recruiting | Sponsor: Intercept Pharmaceuticals | Recruiting ➔ Active, not recruiting

Combination therapy • Enrollment closed • Hepatology • Immunology • Primary Biliary Cholangitis

Study of OCA in Combination With BZF Evaluating Efficacy, Safety and Tolerability in Participants With PBC (clinicaltrials.gov) - P2a | N=60 | Recruiting | Sponsor: Intercept Pharmaceuticals | Trial completion date: Dec 2023 ➔ Aug 2024 | Trial primary completion date: Jan 2023 ➔ Aug 2024

Combination therapy • Trial completion date • Trial primary completion date • Hepatology • Immunology • Primary Biliary Cholangitis

Study of OCA in Combination With BZF Evaluating Efficacy, Safety, and Tolerability in Patients With PBC (clinicaltrials.gov) - P2 | N=75 | Recruiting | Sponsor: Intercept Pharmaceuticals | Trial completion date: Sep 2024 ➔ Dec 2024 | Trial primary completion date: Sep 2023 ➔ Oct 2024

Combination therapy • Trial completion date • Trial primary completion date • Hepatology • Immunology • Primary Biliary Cholangitis