Benzinga | Nov 15, 2021 11:07AM EST

Intercept Announces New Long-Term Data Demonstrating Potential Of Obeticholic Acid To Improve Transplant-Free Survival In Patients With PBC

Intercept Pharmaceuticals, Inc. (NASDAQ:ICPT), a biopharmaceutical company focused on the development and commercialization of novel therapeutics to treat progressive non-viral liver diseases, today announced results from a new analysis examining obeticholic acid's (OCA) potential to improve transplant-free survival in patients with PBC. The data will be featured in a late-breaking podium presentation at The Liver Meeting(r), the Annual Meeting of the American Association for the Study of Liver Diseases (AASLD), which is being held virtually from Friday, November 12 to Monday, November 15, 2021. The analysis was also selected as a "Best of The Liver Meeting" abstract in the Cholestatic and Autoimmune Liver Diseases category.

"This collaborative study used an innovative approach to contribute new understandings about how treatment of patients with PBC with OCA may impact clinical outcomes: we compared patients with PBC who were treated with OCA in the open-label long-term safety extension of the Phase 3 POISE trial, with external controls from two large representative academic-led patient registries. When compared to real-world patient outcome data, the results provide insights into OCA's potential to improve transplant-free survival in patients with PBC treated in a trial setting," said Professor Gideon Hirschfield, FRCP, Ph.D., Lily and Terry Horner Chair in Autoimmune Liver Disease at the University of Toronto. "Data describing the effect of OCA on mortality and need for liver transplant in patients with PBC is eagerly awaited, but such data is inevitably challenging to generate. Notably, when doing this comparison, we found consistent results across the two databases. We hope this analysis can soon be extended to include more patients treated with OCA, and approaches such as this can help the field overcome obstacles to generating meaningful clinical outcome data."

The POISE long-term safety extension (LTSE) study included 209 patients dosed with OCA with a maximum follow-up time of 6.3 years. Propensity score-matched external controls were patients from the Global PBC (n=1,391) and UK-PBC (n=2,138) real-world databases who were diagnosed with PBC and who met POISE clinical trial entry criteria. Patients from the external control databases were untreated or treated with ursodeoxycholic acid (UDCA) with at least one year of follow-up but were not treated with OCA or other therapies. The primary endpoint was time to liver transplantation or death.

In this analysis, 209 patients treated with OCA in the POISE LTSE study had significantly greater transplant-free survival than patients in the external control groups. In the OCA arm, three events were observed versus 146 and 276 events in the Global PBC and UK-PBC external control cohorts, respectively. In a weighted analysis, the hazard ratio favoring OCA was 0.20 (0.06-0.64, p=0.001) in Global PBC and 0.28 (0.09-0.90, p=0.033) in UK-PBC. Thus, patients treated with OCA had a 72% to 80% lower risk of death or liver transplant than the control groups at any time during follow-up. Consistent findings were observed in multiple sensitivity analyses, as well as when testing for the influence of recruitment bias and potential confounding factors such as baseline bilirubin, ALP, AST or ALT, age, PBC duration, UDCA use, diagnosis year and sex.

"The methodology used in this study takes advantage of decades of research to understand the natural history of PBC, and we are thankful to all of the patients and researchers who have contributed data to the Global PBC and UK-PBC study groups," said M. Michelle Berrey, M.D., M.P.H., President of Research & Development and Chief Medical Officer of Intercept. "With a rare, progressive disease like PBC, there are well-known difficulties in conducting long-term, placebo-controlled trials after the approval of a therapeutic agent, so studies like this provide another way to address questions about the impact of OCA on clinical endpoints. The results add to an already substantial body of evidence supporting our belief in OCA's potential to provide benefit for appropriate patients with PBC. We are committed to generating additional long-term data to build on these findings."