Intercept Announces Two Analyses Demonstrating Improvement in Outcomes, Including Transplant-Free Survival, for PBC Patients Treated with OCA to be Presented at AASLD The Liver Meeting® 2022
Efficacy of OCA vs. placebo and external controls accepted as a late-breaker poster
HEROES-US data to be presented in oral session on
Efficacy of Obeticholic Acid (OCA) vs. Placebo and External Control (EC) on Clinical Outcomes in Primary Biliary Cholangitis (PBC) (late-breaker poster,
This analysis assessed the effect of OCA treatment on time to first occurrence of PBC disease progression (hepatic decompensation), liver transplant or death of OCA-treated subjects in the Phase 3b/4 COBALT trial compared to placebo and compared to a non-OCA-treated external control (EC) group created from the Komodo Health
COBALT was a randomized, double-blind, placebo-controlled confirmatory trial designed to assess efficacy and safety of OCA in patients with advanced PBC. As previously disclosed, the study was terminated in
In anticipation of feasibility challenges, the COBALT analysis plan included an EC group as a second comparator arm.
Results from the EC group as-treated analysis showed statistical significance in both the original and the FDA-expanded primary endpoints comparing the OCA-treated subjects in COBALT with the non-OCA-treated patients in EC:
- From the Original Primary Composite Endpoint: 17 (10%) events occurred in subjects in the COBALT OCA arm and 35 (22%) in patients from the non-OCA-treated EC arm (HR=0.39; 95% CI 0.22, 0.69; p<0.01), reflecting a 61% reduction in risk of events at any time during follow-up.
- From the FDA Expanded Primary Endpoint: 28 (17%) events occurred in subjects in the COBALT OCA arm and 46 (28%) in patients from the non-OCA-treated EC arm (HR=0.48; 95% CI 0.30, 0.77; p<0.01), reflecting a 52% reduction in risk of events at any time during follow-up.
“We have long understood the challenges of running placebo-controlled, post-marketing studies, which is why we initiated real-world analyses and leveraged rigorously matched external controls for COBALT to provide additional opportunities to understand the effect of OCA on clinical outcomes in PBC,” said
Results of the HEROES Study: Treatment Efficacy of Obeticholic Acid on Hepatic Real-World Outcomes in Patients with Primary Biliary Cholangitis (oral presentation,
HEROES-US leveraged the
A statistically significant and clinically meaningful reduction in all-cause death, liver transplant, or hospitalization for hepatic decompensation was seen among OCA-treated patients compared to the control group who were not treated with OCA.
- Treatment with OCA resulted in a 63% reduction in relative risk for death, liver transplant and hospitalization for hepatic decompensation (HR=0.37; 95% CI 0.14, 0.75; p<0.001).
- Results were consistent with those observed for comparable endpoints in the POISE trial open-label extension vs. Global PBC patient registry external controls (HR=0.42; 95% CI=0.21, 0.85; p=0.02; Gastroenterology 2022), and the COBALT trial vs. Komodo EC as reported above.
“The HEROES-US study provides clear insights on the effect of OCA on clinical outcomes beyond biochemical measures like alkaline phosphatase,” said Dr.
Intercept is a biopharmaceutical company focused on the development and commercialization of novel therapeutics to treat progressive non-viral liver diseases, including primary biliary cholangitis (PBC) and nonalcoholic steatohepatitis (NASH). For more information, please visit www.interceptpharma.com or connect with the company on Twitter and LinkedIn.
About Primary Biliary Cholangitis
Primary biliary cholangitis (PBC) is a rare, progressive and chronic autoimmune disease that affects the bile ducts in the liver and is most prevalent (approximately 1 in 10,000) in women over the age of 40. PBC causes bile acid to build up in the liver, resulting in inflammation and scarring (fibrosis), which, if left untreated, can lead to cirrhosis, a liver transplant, or death.
COBALT (NCT02308111) was a Phase 3b/4, double-blind, randomized, placebo-controlled, multicenter study that was designed to assess the effect of OCA on clinical outcomes in people living with PBC with an inadequate therapeutic response to UDCA or who were unable to tolerate UDCA. In this trial, eligible people with PBC who were enrolled while on UDCA treatment remained on therapy and were randomized into one of two treatment arms. Patients received placebo or OCA 5 mg daily or 5 mg weekly, based on disease severity, and titrated over the course of the trial to a maximum of OCA 10 mg daily, based on tolerability and biochemical response. Patients were evaluated every three months. The original primary endpoint of the trial was time to first occurrence of any of the following adjudicated events: all-cause death, liver transplant, or other serious liver-related events. Prior to early termination of COBALT, FDA and Intercept agreed on a new primary composite endpoint consisting of a set of expanded, clinically relevant events, including additional decompensation events, as well as clinical events that occur earlier in the disease course and indicate progression toward decompensation.
HEROES is a set of two retrospective studies (NCT05292872, NCT05293938) which leverage real-world datasets to assess the impact of OCA on important clinical outcomes in people living with PBC. The first of these, HEROES-US, leveraged the
This press release contains forward-looking statements (“FLS”), including regarding the results of our clinical studies, and the safety and efficacy of OCA. Important factors could cause actual results to differ materially from the FLS, including further developments regarding understanding of patient outcomes, side effects, or study methodology.
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Source: Intercept Pharmaceuticals, Inc.