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 - Seite 2

• bezafibrate 100 mg IR (B100 IR) (n=11)
• bezafibrate 400 mg IR (B400 IR) (n=11)
• bezafibrate 100 mg IR + OCA 5 mg (OCA5/B100 IR) (n=9)
• bezafibrate 400 mg IR + OCA 5 mg (OCA5/B400 IR) (n=10)

The primary endpoint of both studies is change in alkaline phosphatase (ALP) from baseline to Week 12. The study also assessed percentage change and normalization rates of several serum biomarkers of PBC-induced liver damage, such as alanine transaminase (ALT) and aspartate aminotransferase (AST), as well as markers shown to predict transplant-free survival beyond ALP, including gamma-glutamyl transferase (GGT) and total bilirubin. Safety was assessed by monitoring of adverse events (AEs) and laboratory values.

Efficacy Results

Study 747-213

• OCA5-10/B400 SR showed a −60.6% change in ALP from baseline at week 12 (primary endpoint)
• At week 12, OCA5-10/B400 SR induced biochemical remission, defined as normalization of ALP, GGT, ALT, AST (all ≤ULN) and total bilirubin (≤0.6xULN), in 44.4% of patients compared to 31.6% in B400 SR, 31.6% in OCA5-10/B200 IR and 15.8% in B200 IR
• 66.7% of patients in the OCA5-10/B400 SR arm achieved normalization of ALP (≤ULN) and 100% achieved TB ≤0.6xULN at week 12
• Normalization rates of GGT, ALT and AST (≤ULN) for OCA5-10/B400 SR at week 12 were 58.86%, 94.1% and 82.4% respectively

Study 747-214

• OCA5/B400 IR showed a −65.4% change in ALP from baseline at week 12 (primary endpoint)
• At week 12, OCA5/B400 IR induced biochemical remission in 40.0% of patients compared to 18.2% in B400 IR, 11.1% in OCA5/B100 IR and 9.1% in B100 IR
• 70.0% of patients in the OCA5/B400 IR arm achieved normalization of ALP (≤ULN) and 90.0% achieved TB ≤0.6xULN at week 12
• Normalization rates of GGT, ALT and AST (≤ULN) for OCA/B400 IR at week 12 were 40.0%, 100%, and 90.0%, respectively

Safety Results

The frequency of treatment-emergent adverse events (TEAEs) reported was generally balanced across all arms in both studies. Two severe TEAEs (pruritus [OCA5-10/B400 SR] and hypertension [B200 IR]) occurred in Study 213; the severe TEAE of pruritus led to study discontinuation. One severe TEAE (pruritus, OCA5/B100 IR) occurred in Study 214; no TEAEs led to study discontinuation in Study 214.

The rate of new events of pruritus or worsening of baseline pruritus was very low in the OCA5-10/B400 SR arm of Study 747-213 (2/18 patients). Preliminary data from the OCA5/B400 IR arm of Study 747-214 showed a higher rate of new events of pruritus (7/10 patients), likely due to pharmacokinetic differences between the IR formulation of bezafibrate compared to the SR formulation used in Study 747-213.