Intercept Announces Two Analyses Demonstrating Improvement

Efficacy of OCA vs. placebo and exterior controls accepted as a late-breaker poster

HEROES-US knowledge to be introduced in oral session on Sunday, November 6 

MORRISTOWN, N.J., Nov. 06, 2022 (GLOBE NEWSWIRE) — Intercept Pharmaceuticals, Inc. (Nasdaq: ICPT), a biopharmaceutical firm centered on the event and commercialization of novel therapeutics to deal with non-viral liver ailments, as we speak introduced that outcomes from two analyses assessing the potential of obeticholic acid (OCA) to enhance outcomes for sufferers with major biliary cholangitis (PBC), together with demise, liver transplant and hepatic decompensation, will probably be introduced at The Liver Meeting®, the annual assembly of the American Association for the Study of Liver Diseases (AASLD).

Efficacy of Obeticholic Acid (OCA) vs. Placebo and External Control (EC) on Clinical Outcomes in Primary Biliary Cholangitis (PBC) (late-breaker poster, Monday, Nov. 7)
This evaluation assessed the impact of OCA therapy on time to first prevalence of PBC illness development (hepatic decompensation), liver transplant or demise of OCA-treated topics within the Phase 3b/4 COBALT trial in comparison with placebo and in comparison with a non-OCA-treated exterior management (EC) group created from the Komodo Health U.S. claims database.

COBALT was a randomized, double-blind, placebo-controlled confirmatory trial designed to evaluate efficacy and security of OCA in sufferers with superior PBC. As beforehand disclosed, the research was terminated in December 2021, earlier than it was totally enrolled, for lack of feasibility. The placebo-controlled evaluation of COBALT confirmed no statistically vital distinction in both the Original Primary Composite Endpoint (time to first prevalence of demise, liver transplant or critical liver-related occasions) or the FDA Expanded Primary Endpoint, which additionally included further liver-related occasions.

In anticipation of feasibility challenges, the COBALT evaluation plan included an EC group as a second comparator arm. The EC group, created from Komodo Health claims database, needed to meet COBALT inclusion and exclusion standards and have been weighted utilizing propensity score-derived standardized morbidity ratios (SMRs). The EC group was akin to OCA-treated sufferers in COBALT on all measured baseline variables. Endpoints on this comparability have been the identical as within the major evaluation of the COBALT trial to the extent attainable; nonetheless sure variables, similar to MELD (mannequin for end-stage liver illness), weren’t obtainable within the Komodo database and thus not included.

Results from the EC group as-treated evaluation confirmed statistical significance in each the unique and the FDA-expanded major endpoints evaluating the OCA-treated topics in COBALT with the non-OCA-treated sufferers in EC:

• From the Original Primary Composite Endpoint: 17 (10%) occasions occurred in topics within the COBALT OCA arm and 35 (22%) in sufferers from the non-OCA-treated EC arm (HR=0.39; 95% CI 0.22, 0.69; p<0.01), reflecting a 61% discount in danger of occasions at any time throughout follow-up.
• From the FDA Expanded Primary Endpoint: 28 (17%) occasions occurred in topics within the COBALT OCA arm and 46 (28%) in sufferers from the non-OCA-treated EC arm (HR=0.48; 95% CI 0.30, 0.77; p<0.01), reflecting a 52% discount in danger of occasions at any time throughout 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,” stated M. Michelle Berrey, M.D., MPH, President, Research & Development and Chief Medical Officer of Intercept. “We believe that the real-world data we have generated to date demonstrate long-term benefits to people with PBC who are receiving OCA, specifically improved event-free survival, which we know to be the most important treatment goal for patients and clinicians.”

Results of the HEROES Study: Treatment Efficacy of Obeticholic Acid on Hepatic Real-World Outcomes in Patients with Primary Biliary Cholangitis (oral presentation, Sunday, Nov. 6)
HEROES-US leveraged the Komodo Health database in a totally real-world research to evaluate the potential advantages of OCA therapy on demise, liver transplant and hospitalization for hepatic decompensation in PBC sufferers with compensated liver illness. The research checked out a pre-defined group of sufferers with PBC who have been handled with OCA and a comparable group of PBC sufferers who have been eligible, however who weren’t handled with OCA. Characteristics of sufferers who initiated therapy with OCA have been SMR-weighted to OCA-eligible sufferers not handled with OCA.

A statistically vital and clinically significant discount in all-cause demise, liver transplant, or hospitalization for hepatic decompensation was seen amongst OCA-treated sufferers in comparison with the management group who weren’t handled with OCA.

• Treatment with OCA resulted in a 63% discount in relative danger for demise, liver transplant and hospitalization for hepatic decompensation (HR=0.37; 95% CI 0.14, 0.75; p<0.001).
• Results have been in keeping with these noticed for comparable endpoints within the POISE trial open-label extension vs. Global PBC affected person registry exterior 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,” stated Dr. Kris V. Kowdley, Director of Liver Institute Northwest, and Professor on the Elson S. Floyd College of Medicine, Washington State University. “Furthermore, these data underscore results we’ve seen across multiple analyses, building on the robust body of evidence showing the positive impact of long-term treatment with OCA.”

About Intercept 
Intercept is a biopharmaceutical firm centered on the event and commercialization of novel therapeutics to deal with progressive non-viral liver ailments, together with major biliary cholangitis (PBC) and nonalcoholic steatohepatitis (NASH). For extra info, please go to www.interceptpharma.com or join with the corporate on Twitter and LinkedIn.

About Primary Biliary Cholangitis 
Primary biliary cholangitis (PBC) is a uncommon, progressive and power autoimmune illness that impacts the bile ducts within the liver and is most prevalent (roughly 1 in 10,000) in ladies over the age of 40. PBC causes bile acid to construct up within the liver, leading to irritation and scarring (fibrosis), which, if left untreated, can result in cirrhosis, a liver transplant, or demise.

About COBALT 
COBALT (NCT02308111) was a Phase 3b/4, double-blind, randomized, placebo-controlled, multicenter research that was designed to evaluate the impact of OCA on scientific outcomes in individuals dwelling with PBC with an insufficient therapeutic response to UDCA or who have been unable to tolerate UDCA. In this trial, eligible individuals with PBC who have been enrolled whereas on UDCA therapy remained on remedy and have been randomized into certainly one of two therapy arms. Patients acquired placebo or OCA 5 mg every day or 5 mg weekly, primarily based on illness severity, and titrated over the course of the trial to a most of OCA 10 mg every day, primarily based on tolerability and biochemical response. Patients have been evaluated each three months. The unique major endpoint of the trial was time to first prevalence of any of the next adjudicated occasions: all-cause demise, liver transplant, or different critical liver-related occasions. Prior to early termination of COBALT, FDA and Intercept agreed on a brand new major composite endpoint consisting of a set of expanded, clinically related occasions, together with further decompensation occasions, in addition to scientific occasions that happen earlier within the illness course and point out development towards decompensation.

About HEROES 
HEROES is a set of two retrospective research (NCT05292872, NCT05293938) which leverage real-world datasets to evaluate the influence of OCA on essential scientific outcomes in individuals dwelling with PBC. The first of those, HEROES-US, leveraged the Komodo Health claims database, linked by way of Datavant tokenization to Quest and LabCorp laboratory knowledge and the Social Security Death Index, to match scientific outcomes (outlined as all-cause demise, liver transplant, or hospitalization for hepatic decompensation) of PBC sufferers who have been handled with OCA with PBC sufferers who have been eligible, however not handled with OCA. In the evaluation, sufferers have been required to have one inpatient PBC declare, or two outpatient claims separated by greater than sooner or later; a historical past of UDCA use; an elevated ALP and/or complete bilirubin; and meet comorbidity exclusion standards. Propensity scores and standardized morbidity ratios have been used to weight cohorts to make sure comparable baseline scientific and demographic traits, comorbidities, illness and therapy historical past. This trial was designed and executed following FDA’s draft steering on use of real-world proof to assist regulatory decision-making for drug and organic merchandise.

Forward-Looking Statements 
This press launch comprises forward-looking statements (“FLS”), together with relating to the outcomes of our scientific research, and the security and efficacy of OCA. Important elements may trigger precise outcomes to vary materially from the FLS, together with additional developments relating to understanding of affected person outcomes, unwanted side effects, or research methodology.

Contact

For extra details about Intercept, please contact:

For traders:
Nareg Sagherian, Executive Director, Global Investor Relations
[email protected] 

For media:
Karen Preble, Executive Director, Global Corporate Communications
[email protected]