Intercept Unveils Six-Month OCA-Bezafibrate PBC Therapy Results at EASL 2024

Intercept Pharmaceuticals, Inc., a biopharmaceutical firm based in Morristown, N.J., and a subsidiary of Alfasigma S.p.A., has disclosed promising six-month data from its ongoing Phase 2 study 747-213. This study evaluates the combination therapy of obeticholic acid (OCA) and bezafibrate in patients with primary biliary cholangitis (PBC). The data was presented at the European Association for the Study of the Liver (EASL) Congress 2024 in Milan, Italy.

The primary focus of the study is to assess the potential of this combination therapy to normalize various serum biomarkers, which are indicative of improved survival rates without the need for transplants or the occurrence of liver decompensation in PBC patients. David Jones, a Professor of Liver Immunology at Newcastle University, emphasized that the combination therapy could set a new standard for efficacy in PBC treatment, with over two-thirds of patients showing significant biochemical remission.

In the study, patients were randomized into four groups, each receiving different dosage combinations of bezafibrate and OCA alongside ongoing ursodeoxycholic acid (UDCA) treatment, if applicable. The four groups included:
- Bezafibrate 200 mg immediate release (B200 IR) (n=19)
- Bezafibrate 400 mg sustained release (B400 SR) (n=19)
- Bezafibrate 200 mg IR + OCA 5 mg titrated to 10 mg at Week 4 (OCA/B200 IR) (n=19)
- Bezafibrate 400 mg SR + OCA 5 mg titrated to 10 mg at Week 4 (OCA/B400 SR) (n=18)

After the 12-week double-blind treatment period, the OCA-bezafibrate dosages were optimized in a long-term safety extension phase. The most significant biochemical response was observed in the OCA/B400 SR group. Key findings at the six-month mark included:
- A 65.3% reduction in alkaline phosphatase (ALP) levels, with 61.1% of patients achieving ALP levels less than or equal to the upper limit of normal (ULN), and 77.8% experiencing a 40% reduction from baseline.
- A 27.6% reduction in total bilirubin (TB), with 83.3% of this group achieving TB levels ≤0.6 x ULN.
- Significant percentage reductions in other liver enzymes: alanine aminotransferase (ALT) by 41.9%, aspartate aminotransferase (AST) by 16.1%, and gamma-glutamyl transferase (GGT) by 81.6%.
- High normalization rates of ALT, AST, and GGT at 83.3%, 77.8%, and 72.2%, respectively.
- Biochemical remission was achieved in 66.7% of patients, defined by a 40% change or normalization in ALP, GGT, ALT, and AST levels, as well as TB ≤0.6 x ULN.

Additionally, the OCA/B400 SR combination showed the most significant improvements in GLOBE and UK-PBC scores, prognostic tools used to assess long-term outcomes in PBC patients. Adverse events were generally balanced across all treatment cohorts.

Sangeeta Sawhney, Senior Vice President and Head of U.S. Research & Development at Intercept, noted that the combination therapy could redefine the treatment benefits for PBC and expressed optimism about progressing to Phase 3 trials.

Intercept is continuing its research with two ongoing Phase 2 studies to explore various therapeutic doses and formulations of the OCA and bezafibrate combination.

About the Investigational OCA-bezafibrate Combination

OCA, marketed as Ocaliva in the U.S. for treating PBC, is a farnesoid X receptor (FXR) agonist. Bezafibrate, not approved in the U.S., is a pan-peroxisome proliferator-activated receptor (pan-PPAR) agonist. Targeting both FXR and PPAR pathways simultaneously may offer enhanced efficacy in treating cholestatic liver diseases such as PBC. The combination therapy remains investigational, with its safety and efficacy yet to be fully established.

About Primary Biliary Cholangitis

PBC is a rare autoimmune disease affecting the liver's bile ducts, leading to inflammation, scarring, and potentially cirrhosis, liver transplant, or death if untreated. It predominantly affects women over 40, with a prevalence of about 1 in 10,000.

About Ocaliva 

Ocaliva, an FXR agonist, is approved in the U.S. for treating adults with PBC without cirrhosis or with compensated cirrhosis who do not show evidence of portal hypertension. It is used either in combination with UDCA for inadequate responders or as monotherapy for those intolerant to UDCA.

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