LY-2562175

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. Your email address will not be published. Required fields are marked * Comment * Name * Email * Website

The money continues to flow for private obesity and MASH drug developers. The latest pool of capital is headed to a Shanghai biotech called Cascade Pharmaceuticals. The company disclosed a nearly 500 million yuan (about $72 million) financing round via an announcement on WeChat this week. The biotech, founded in December 2017, previously disclosed a 140 million yuan round in August 2023 and two “nearly” 100 million yuan rounds in 2020 and 2022. While many Chinese drug developers have forged partnerships with Western biopharmas during a flurry of cross-border deals, it appears Cascade is developing its pipeline independently and has global rights to all of the experimental medicines listed on its website. Cascade has conducted clinical trials in both China and the US. The Chinese drug development sector has ballooned in recent years thanks to a spike in R&D on new medicines, a surge in the number of clinical trials, and a proliferation of new startups. Multiple Western pharmaceutical companies have gone to China for obesity assets. On Tuesday, Kailera’s China partner Hengrui reported oral GLP-1 data, and AstraZeneca also disclosed clinical data for an oral GLP-1 asset that the UK pharma licensed from China and US biotech Eccogene. Cascade is in Phase 3 with an FXR-targeted small molecule called linafexor, or CS0159. The investigational medicine is in Phase 3 in China in primary biliary cholangitis. Linafexor is also in earlier stages of clinical testing for metabolic dysfunction-associated steatohepatitis, inflammatory bowel disease, obesity and primary sclerosing cholangitis. Cascade said the asset has completed Phase 2 for MASH in the US. FXR is a target quite familiar to the MASH field. The FDA rejected Intercept Pharmaceuticals’ Ocaliva for MASH, but others are still delving into the mechanism. Eli Lilly paid $9 million upfron t last winter for access to an FXR agonist in development for MASH and ulcerative colitis. MASH has been a hot dealmaking area for drugmakers since Madrigal Pharmaceuticals was able to secure the first FDA treatment approval for the fatty liver disease in March 2024. Madrigal’s Rezdiffra is a partial agonist of the thyroid hormone beta-receptor, or THR-β. Cascade has a program for that target as well. The biotech’s THR-β tablet, codenamed CS060380, recently entered Phase 2 for MASH in China. Cascade has previously said its candidate is “highly specific to liver tissue” and had “superior preclinical data compared to MGL-3196 [Rezdiffra].” Cascade’s work in obesity also includes small molecule and peptide “triple G” candidates that go after receptors of GLP-1, GIP and GCG. Lilly and others are also developing triple G medicines in the race to create more powerful weight loss medications. The company also has an asset called CS060304 in clinical testing for people with elevated levels of LDL-C, commonly referred to as “bad” cholesterol. Cascade said it works on “nuclear receptors” and G protein-coupled receptors. GPCRs are a common area for drug developers, including those in obesity.