P1744 - 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

Meha Ballard, RN, MSN¹, David E. Jones, PhD², Alexandre Louvet, MD, PhD³, Christophe Corpechot, MD⁴, Vaclav Hejda, MD, PhD⁵, Heng Zou, ¹, Antonio Civitarese, PhD⁶, Alejandra Villamil, MD⁷, Frederick Nevens, MD, PhD^8
1Intercept Pharmaceuticals, Inc., Morristown, NJ; ²Newcastle University, Newcastle upon Tyne, England, United Kingdom; ³University Hospital, Lille, Nord-Pas-de-Calais, France; ⁴Reference Centre for Inflammatory Biliary Diseases and Auto-Immune Hepatitis, Saint-Antoine Hospital, Paris, Ile-de-France, France; ⁵University Hospital, Pilsen, Plzensky kraj, Czech Republic; ⁶Intercept Pharmaceuticals Inc., Morristown, NJ; ⁷Hospital Italiano de Buenos Aires, Buenos Aires, Buenos Aires, Argentina; ⁸University Hospital KU Leuven, Leuven, Vlaams-Brabant, Belgium

Introduction: Obeticholic acid (OCA) and bezafibrate (BZF) have each improved serum biomarkers of primary biliary cholangitis (PBC)–related liver damage. We assessed the effects of OCA + BZF vs BZF alone on serum biomarker levels and safety/tolerability in patients (pts) with PBC who had inadequate response or intolerance to ursodeoxycholic acid.

Methods: This double-blind (DB) phase 2 trial randomized pts 1:1:1:1 to once-daily oral BZF 200 mg (B200) immediate release (IR), BZF 400 mg (B400) sustained release (SR), OCA 5 mg titrated to 10 mg at week 4 + BZF 200 mg IR (OCA/B200 IR), or OCA 5 mg titrated to 10 mg at week 4 + BZF 400 mg SR (OCA/B400 SR) in a 12-week DB treatment (tx) period. Pts continued their original tx assignment for an additional 12 weeks before transitioning to the planned phase 3 dose in a 96-week open-label long-term safety extension (LTSE). Here, we present data from month 6 (12-week DB tx period + DB follow-up period). Change from baseline and normalization rate of alkaline phosphatase (ALP; ≤ upper limit of normal [ULN]) and total bilirubin (TB; ≤ 0.6 x ULN) were assessed. Biochemical remission was defined as ≥ 40% reduction in ALP or ALP ≤ ULN; gamma-glutamyl transferase, alanine aminotransferase, and aspartate aminotransferase ≤ ULN; and TB ≤ 0.6 x ULN. GLOBE and UK-PBC scores estimated the risk of death and liver transplantation. Safety was assessed by tx-emergent adverse events (TEAEs).

Results: 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. TEAEs were generally balanced across cohorts. In the OCA/B400 SR cohort, 1 pt discontinued due to a serious TEAE of pruritus. The rate of new events of pruritus with OCA/B400 SR was low (11.1%). OCA/B400 SR demonstrated the greatest percentage reductions in total (19.6%) and low-density lipoprotein cholesterol (18.7%).

Discussion: OCA + BZF is generally well tolerated and has therapeutic potential to normalize 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. The data support phase 3 development of the SR formulation of BZF with low doses of OCA.



Disclosures:


Meha Ballard, RN, MSN¹, David E. Jones, PhD², Alexandre Louvet, MD, PhD³, Christophe Corpechot, MD⁴, Vaclav Hejda, MD, PhD⁵, Heng Zou, ¹, Antonio Civitarese, PhD⁶, Alejandra Villamil, MD⁷, Frederick Nevens, MD, PhD⁸. P1744 - 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 Annual Scientific Meeting Abstracts. Philadelphia, PA: American College of Gastroenterology.