Intercept Pharmaceuticals, Inc. announced new data from a sub-analysis of the landmark Phase 3 POISE trial evaluating the impact of obeticholic acid (OCA) on achievement of gamma-glutamyl transferase (GGT) <3.2×upper limit of normal (ULN) and alkaline phosphatase (ALP) <1.5×ULN for the treatment of primary biliary cholangitis (PBC). This analysis suggests OCA?s potential to reduce GGT, in addition to the well-known effects on ALP levels, below the biochemical thresholds that are prognostic for worsening clinical outcomes. These data will be presented on November 13, 2023, at the American Association for the Study of Liver Diseases?

(AASLD) The Liver Meeting® in Boston. In the study, patients with PBC who were receiving a stable dose of ursodeoxycholic acid (UDCA) or who were unable to tolerate UDCA were randomized to receive placebo, OCA 5-10 mg (OCA titration), or OCA 10 mg daily. For the OCA 5-10 mg group, OCA 5 mg was titrated to 10 mg at 6 months based on tolerability and biochemical response.

A 12-month double-blind (DB) period was followed by a 5-year optional open-label extension (OLE), in which all patients were initially treated with OCA 5 mg daily for the first 3 months; every 3 months thereafter, patients had the option to increase the dose up to 10 mg. Serum GGT and ALP levels were assessed at baseline and every 3 months through the 5-year follow-up. Hepatocyte injury causes GGT to be released into the blood.

Elevated GGT in the setting of elevated ALP and other liver enzyme abnormalities is a marker for hepatobiliary disorder. The goal of this sub-analysis was to evaluate the proportion of patients receiving OCA who achieved and sustained GGT <3.2×ULN and ALP <1.5×ULN. Results include: In the double-blind (DB) intent-to-treat population (N=203), the proportion of responders was significantly greater at each time point in both OCA cohorts compared with placebo, with the highest responder rates observed in the OCA 10 mg group.

In the OCA titration group, 17% (11/66) were responders at DB Months 9 and 12. In the OCA 10 mg group, the highest responder rate was observed at DB Month 9 (31% [21/68]), followed by DB Month 12 (26% [18/68]). In the open-label extension (OLE) intent-to-treat population (N=119), the proportion of responders generally increased over time, ranging from 18% (22/119) at OLE Month 3 to 38% (35/91) at OLE Month 51.

At OLE Month 60, 37% (17/46) were responders. The POISE trial studied the safety and efficacy of once-daily treatment with Ocaliva in PBC patients with an inadequate therapeutic response to, or who were unable to tolerate, ursodeoxycholic acid (UDCA). There were 217 patients randomized to one of three groups in the trial: placebo, OCA 10 mg, or OCA 5 mg for six months titrated to 10 mg based on clinical response.

Seven subjects did not participate in the open-label extension and were not included in the current study. Patients completing the double-blind phase had the option to continue in an open-label extension (OLE) phase for a maximum of five additional years, during which all patients received treatment with OCA 5-10 mg once daily. Of the 198 patients who completed the double-blind phase, more than 95% continued in the long-term safety extension phase of the trial for up to 5 years.