Intercept Announces Publication Of Meta-Analysis From The Global PBC Study Group In Gastroenterology

Intercept Pharmaceuticals, Inc. ICPT (Intercept), a clinical stage biopharmaceutical company focused on the development and commercialization of novel therapeutics to treat chronic liver and intestinal diseases, announced today the publication of the meta-analysis performed by the Global Primary Biliary Cirrhosis Study Group (Global PBC Study Group) in the December issue of Gastroenterology. In the largest meta-analysis of individual PBC patient data conducted to date, researchers confirmed that levels of ALP and bilirubin predicted clinical outcomes of patients with PBC. Of the 4,845 patients included in the analysis, 1,118 reached a clinical outcome defined as liver transplantation or death. For the first time, the researchers reported a log-linear association between ALP values and liver transplant-free survival. At one year after study enrollment, an ALP level of two times upper limit of normal (ULN) best predicted patient outcome (C statistic, 0.71) but not significantly better than other lower ALP thresholds such as 1.67 times ULN. Of patients with ALP levels less than or equal to two times ULN, 84% survived for over a ten year follow-up period compared with 62% of those with levels exceeding two times ULN (p < 0.0001). Elevated bilirubin levels were strongly predictive of a worse prognosis and only 41% of such patients had not had a liver transplant or died over the subsequent 10 years compared with 86% of patients with normal bilirubin levels (p < 0.0001). The Global PBC Study Group analysis also showed that ALP and bilirubin were correlated with clinical outcomes consistently over time and in all the patient subgroups evaluated. Specifically, ALP was predictive of transplant-free survival in PBC patients both on and off standard of care treatment, those with histologically advanced or early stage disease, patients 45 years or younger or over 45 years at the time of diagnosis, female or male, and irrespective of the year of diagnosis. "This study represents the largest international collaboration in PBC and provided us with a wealth of data supporting the use of this biochemical endpoint for therapeutic clinical trials," said senior author Bettina Hansen, Ph.D., Department of Gastroenterology and Hepatology, Erasmus University Medical Centre in Rotterdam. "But the key takeaway from this analysis for everyday clinical practice is that the lower a patient's ALP level and having a normal bilirubin level correlate with an improved prognosis for patients with PBC." The Global PBC Study Group consists of 15 leading PBC centers in eight countries that contributed to a clinical outcomes database of more than 6,000 patients with PBC. Data were analyzed under the direction of Dr. Bettina Hansen, Dr. Willem J. Lammers, Dr. Henk van Buuren and colleagues at Erasmus University Medical Centre in Rotterdam, the Netherlands. Intercept was a sponsor of this independent academic research program but was not involved in the study design, data collection, analysis or publication. "We believe the Global PBC Study Group's research supports the clinical relevance of a primary endpoint based on ALP and bilirubin in clinical trials of patients with PBC," said David Shapiro, M.D., Chief Medical Officer of Intercept. "More broadly, it should enhance monitoring of disease progression and lead to better dialogue between clinicians and patients." "The work done by the Global PBC Study Group exemplifies the value of such cooperative initiatives in generating large clinical datasets that may provide evidence for the utility of proposed surrogate endpoints and a better understanding of the natural history of diseases such as PBC," said Mark Pruzanski, M.D., CEO of Intercept. "We hope the Global PBC Study Group's work continues in the future and would like to thank all of the researchers and patients involved in making such an invaluable contribution to the medical community's understanding of this rare disease."