Intercept Pharma Terminates INT-787 Trial

Intercept Pharmaceuticals has terminated its Phase II proof-of-concept trial of INT-787, a selective farnesoid X receptor (FXR) agonist, in severe alcohol-associated hepatitis, according to a ClinicalTrials.gov registry update. The NCT05639543 record, known as the FRESH (FXR Effect on Severe Alcohol-Associated Hepatitis) study, lists overall status as terminated. According to the posting, the termination reflects a "business decision" that was taken on March 31, 2026, and reflects the fact there was "no clear evidence of potential benefit of INT-787 in sAH", although there were no safety concerns related to the molecule.

The FRESH study was a randomized, double-blind, placebo-controlled, multicenter, dose-escalation trial designed to generate proof-of-concept data on INT-787 in patients hospitalized with severe alcohol-associated hepatitis. Enrollment reached 67 participants across sites in the United States, France, and the United Kingdom, including academic centers such as Mayo Clinic, Beth Israel Deaconess Medical Center, King's College Hospital, and Hôpital Beaujon. Eligible patients were aged 18 to 65, carried a clinical diagnosis of severe alcohol-associated hepatitis defined by excess alcohol use, serum total bilirubin above 3.0 mg/dL, AST at or above 50 U/L, and an AST-to-ALT ratio of at least 1.5, with Maddrey's Discriminant Factor of 32 or greater. The trial excluded patients with concurrent viral hepatitis, hepatocellular carcinoma, prior liver transplantation, or recent obeticholic acid use.

INT-787 is a next-generation FXR agonist developed by Intercept as a follow-on to obeticholic acid, the company's first-generation FXR agonist marketed as Ocaliva for primary biliary cholangitis. FXR activation modulates bile acid homeostasis, hepatic inflammation, and fibrosis through transcriptional regulation of downstream targets including fibroblast growth factor 19 and small heterodimer partner. In the context of alcohol-associated hepatitis, FXR agonism was hypothesized to attenuate the inflammatory cascade and improve hepatocellular function, with the Lille score — a validated early predictor of corticosteroid response and 28-day mortality — serving as the primary readout of biological activity.

The FRESH study was initiated in December 2022, with a planned primary completion date of February 2026. The registry record was last updated in April 2026, and the termination status was verified as of April 1, 2026, placing the INT-787 clinical trial termination in the same period as the study's nominal completion window.

Intercept was acquired by Italian pharmaceutical group Alfasigma in late 2023, a transaction premised on building a US presence in hepatology. The acquisition followed years of regulatory difficulty for obeticholic acid in nonalcoholic steatohepatitis, where the FDA declined to grant accelerated approval. That setback was compounded when Ocaliva's confirmatory trial in primary biliary cholangitis failed to demonstrate clinical benefit on hard endpoints, ultimately leading to the voluntary withdrawal of Ocaliva from the US market in November 2025. The withdrawal eliminated Intercept's only commercial revenue stream and triggered a restructuring.

At the time of the restructuring, INT-787 and the FRESH study were publicly identified as the company's primary remaining clinical focus. The subsequent termination of that study leaves Intercept and its parent Alfasigma without an active late-stage clinical program in the United States, a material change from the strategic rationale that underpinned the acquisition. Whether Alfasigma intends to continue INT-787 development in any form, or pursue alternative hepatology assets, has not been disclosed in the available evidence.

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