Intercept Pharmaceuticals, Inc. announced new results from a planned interim analysis of its ongoing Phase 2 study 747-213 assessing improvements in serum biomarkers of hepatic function, cholestasis and inflammation in patients with primary biliary cholangitis (PBC) after treatment with an investigational combination of obeticholic acid (OCA) and bezafibrate. Results from the full interim data set, shared in a podium presentation June 23, 2023 at the European Association for the Study of the Liver (EASL) Congress 2023 in Vienna, Austria, showed that the combination of OCA 5-10 mg and bezafibrate 400 mg was effective in normalizing multiple biochemical markers associated with PBC-induced liver damage. In this planned interim analysis from the first of two Phase 2 studies, 62 patients with PBC were randomized to receive 12 weeks of once-daily oral therapy in addition to ongoing ursodeoxycholic acid (UDCA) treatment (if any) in one of four treatment arms: bezafibrate 200 mg (B200) (n=16); OCA 5 mg titrated to 10 mg at week 4 + bezafibrate 200 mg (OCA5-10/B200) (n=16); bezafibrate 400 mg (B400) (n=15) and OCA 5 mg titrated to 10 mg at week 4 + bezafibrate 400 mg (OCA5-10/B400) (n=15). The goal of this interim analysis was to assess improvements in serum biomarkers of PBC-induced liver damage including alanine transaminase (ALT) and aspartate aminotransferase (AST) as well as markers shown to predict transplant-free survival including alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT) and total bilirubin. Safety was assessed by monitoring of adverse events (AEs) and laboratory values. The primary efficacy endpoint of Study 747-213 is change in ALP from baseline to week 12. Efficacy: Biochemical remission, defined as normalization of ALP, GGT, ALT, AST (all =ULN) and total bilirubin (=0.6xULN), was induced in 58% of patients on OCA5-10/B400 at 12 weeks vs 7% (B200), 27% (B400) and 31% (OCA5-10/B200) in the other treatment arms. Further, patients in the OCA5-10/B400 arm experienced consistently high levels of normalization of individual biomarkers ALP (75% normalized), GGT (75% normalized), total bilirubin (=0.6xULN, 100% normalized), ALT (100% normalized) and AST (92% normalized). The lower target for total bilirubin was selected as it is associated with the lowest risk for liver transplant or death. Patients in the OCA5-10/B400 arm demonstrated the highest rates of reduction from baseline in ALP, ALT, total bilirubin and GGT with a clear dose response seen in total bilirubin and GGT. Safety: Treatment-emergent adverse events (TEAEs) were generally balanced across all arms (8 in B200, 11 in OCA5-10/B200, 12 in B400, 9 in OCA5-10/B400) with the majority being mild and not related to study drug. No deaths occurred in the study. Pruritus events were low across all study arms with the lowest rate in the OCA5-10/B400 arm (2 events, 13.3%). Observed pruritus in the other arms were 4 events (25%) in B200; 4 events (25%) in OCA5-10/B200; and 3 events (20%) in B400. One serious treatment-related pruritus TEAE leading to discontinuation was reported in the OCA5-10/B400 arm.
There was a reduction from baseline in mean cholesterol levels at 4 weeks in the combination arms and relative to the active control, bezafibrate. Patients in the two OCA-bezafibrate treatment arms demonstrated the largest reductions in cholesterol at 12 weeks with a clear dose response.