Intercept Unveils New Phase 3 POISE Data on OCA's Impact on Liver Biomarkers and Fibrosis in PBC at DDW 2024

Intercept Pharmaceuticals, Inc., a subsidiary of Alfasigma S.p.A., has announced promising results from its Phase 3 POISE study on primary biliary cholangitis (PBC) during Digestive Disease Week® (DDW) 2024 held in Washington, D.C. The study focused on the efficacy of obeticholic acid (OCA) in normalizing liver enzymes and reducing liver fibrosis indicators.

The POISE study evaluated the safety and efficacy of daily OCA treatment in PBC patients who showed inadequate response to or were intolerant of ursodeoxycholic acid (UDCA). Participants were divided into three groups: those receiving a placebo, those given OCA 10 mg, and those given OCA 5 mg titrated to 10 mg based on clinical response. The study included a 12-month double-blind phase and an extended safety phase lasting up to five years. The primary endpoint was achieving both an alkaline phosphatase (ALP) level less than 1.67 times the upper limit of normal (ULN) with a reduction of at least 15% from baseline and a normal bilirubin level.

Key findings from the sub-analyses presented at DDW 2024 include the impact of OCA on alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, as well as the aminotransferase to platelet ratio index (APRI), a predictor of liver fibrosis progression. Both treatment groups (OCA 10 mg and OCA 5-10 mg) significantly reduced ALT and AST levels compared to the placebo group, with reductions observed as early as two weeks into the treatment.

For ALT, the OCA 10 mg and OCA 5-10 mg groups had least squares (LS) mean changes from baseline of -25 U/L and -21 U/L, respectively, compared to -5 U/L in the placebo group. After 12 months, ALT normalization was achieved in 33% and 29% of patients in the OCA 10 mg and OCA 5-10 mg groups, respectively, compared to just 10% in the placebo group. Among those who met the primary endpoint at Month 12, 44% and 34% of patients in the OCA 10 mg and OCA 5-10 mg groups, respectively, achieved normal ALT levels, whereas none in the placebo group did.

Regarding AST, the OCA 10 mg and OCA 5-10 mg groups achieved LS mean changes from baseline of -15 U/L and -13 U/L, respectively, while the placebo group showed a +1 U/L change. AST normalization was observed in 30% and 23% of patients in the OCA groups, respectively, compared to 10% in the placebo group. Among those reaching the primary endpoint at Month 12, 47% and 31% of patients in the OCA 10 mg and OCA 5-10 mg groups, respectively, had normal AST levels, with none in the placebo group achieving this.

Additionally, a post hoc analysis highlighted the significant reduction in APRI scores among OCA-treated patients, reinforcing OCA's potential in managing liver fibrosis.

Dr. Robert R. Gish from Loma Linda University emphasized the importance of these findings, stating that assessing multiple liver biomarkers can better inform PBC treatment decisions. Sangeeta Sawhney, Senior Vice President and Head of U.S. Research & Development at Intercept, noted that these results build on years of real-world experience and demonstrate the benefits of OCA in PBC treatment.

The POISE trial involved 217 patients, with 198 continuing into a long-term extension phase. Over 95% of those who completed the double-blind phase remained in the safety extension phase for up to five years. This extensive study underlines OCA's role in treating PBC, particularly for patients unresponsive or intolerant to UDCA.