Pemvidutide

Granted FDA Breakthrough Therapy Designation for MASH in January 2026. Phase 3 program initiation planned for 2026. End-of-Phase 2 meeting with FDA completed successfully.

Effective: January 2026

A dual GIP/GLP-1 receptor agonist FDA-approved for type 2 diabetes, weight management, and MASH with liver fibrosis.

A GLP-1 receptor agonist FDA-approved for type 2 diabetes and chronic weight management.

An investigational triple agonist (GIP/GLP-1/glucagon) studied for obesity and metabolic disease.

A dual GLP-1/glucagon receptor agonist with FDA Breakthrough Therapy designation for MASH and Priority Review NDA filed February 2026. Phase 3 SYNCHRONIZE-1 reported 16.6% weight loss at 76 weeks; approval possible Q3 2026.

Efocipegtrutide (Hanmi code HM15211) is an investigational, long-acting, once-weekly GLP-1/GIP/glucagon 'triple' receptor agonist being developed primarily for metabolic dysfunction-associated steatohepatitis (MASH, formerly NASH) rather than obesity alone. It is built on Hanmi's LAPSCovery platform as a chemical conjugate of a chimeric tri-agonist peptide (TA15211) fused to a human IgG4 Fc fragment, which extends its half-life via FcRn-mediated recycling and enables weekly subcutaneous dosing. By adding glucagon-receptor activation to the GLP-1/GIP dual mechanism, efocipegtrutide is designed to combine appetite suppression and glycemic control with increased energy expenditure and direct hepatic anti-steatotic, anti-inflammatory, and anti-fibrotic effects. In a Phase 1b/2a study in obese subjects with non-alcoholic fatty liver disease, 12 weeks of treatment reduced liver fat by roughly 20% to 59% (dose-dependent, MRI-PDFF) versus about 6% on placebo. It has FDA Fast Track designation for MASH and orphan-drug designations from the FDA and EMA for primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC), and idiopathic pulmonary fibrosis (IPF). The 52-week adaptive Phase 2 HM-TRIA-201 study (NCT04505436) in biopsy-confirmed MASH with fibrosis is the pivotal read the field is watching.

Pegozafermin (development code BIO89-100) is an investigational, long-acting analog of fibroblast growth factor 21 (FGF21) being developed for metabolic dysfunction-associated steatohepatitis (MASH, formerly NASH) and for severe hypertriglyceridemia (SHTG). Originally developed by 89bio and acquired by Roche in a deal announced in September 2025 (about $2.4 billion upfront and up to roughly $3.5 billion including a contingent value right), it uses site-specific glycoPEGylation to extend the very short half-life of native FGF21 to roughly 55-100 hours, enabling once-weekly or once-every-two-weeks subcutaneous dosing. FGF21 is a metabolic hormone that acts on liver, fat, and other tissues to improve insulin sensitivity, lower triglycerides, and exert direct anti-fibrotic and anti-inflammatory effects. In the Phase 2b ENLIVEN trial in biopsy-confirmed F2-F3 MASH, the 44 mg every-two-weeks dose produced at least a one-stage fibrosis improvement without worsening of MASH in about 27% of patients versus 7% on placebo, and MASH resolution without worsening of fibrosis in about 26% versus 2% on placebo, with benefits sustained through week 48. Pegozafermin holds FDA Breakthrough Therapy designation and EMA PRIME status for MASH and has advanced into the Phase 3 ENLIGHTEN program (ENLIGHTEN-Fibrosis in non-cirrhotic F2-F3 MASH and ENLIGHTEN-Cirrhosis in compensated F4 cirrhosis), plus the Phase 3 ENTRUST trial in SHTG.

Efruxifermin (development codes EFX, AKR-001; originally AMG 876) is an investigational, once-weekly, subcutaneously injected analog of the metabolic hormone fibroblast growth factor 21 (FGF21) being developed by Akero Therapeutics for metabolic dysfunction-associated steatohepatitis (MASH, formerly NASH), including both pre-cirrhotic fibrosis and compensated (F4) cirrhosis. It is a bivalent Fc-FGF21 fusion protein - two engineered FGF21 sequences fused to a human immunoglobulin (IgG1) Fc domain - a design distinct from the glycoPEGylation used by its main FGF21-class rival, pegozafermin. The Fc fusion extends the very short half-life of native FGF21 to support once-weekly dosing while preserving agonism at FGF receptors (FGFR1c/2c/3c) together with the co-receptor beta-Klotho. In the 96-week Phase 2b HARMONY trial in biopsy-confirmed F2-F3 MASH, at least a one-stage improvement in fibrosis without worsening of MASH was reached by about 75% of patients on 50 mg and 46% on 28 mg versus 24% on placebo (published in The Lancet, August 2025). In the Phase 2b SYMMETRY trial in compensated MASH cirrhosis, about 39% of 50 mg patients with paired week-96 biopsies achieved reversal of cirrhosis without worsening of MASH versus 15% on placebo (published in the New England Journal of Medicine). Efruxifermin holds FDA Breakthrough Therapy designation and has advanced into the Phase 3 SYNCHRONY program (SYNCHRONY Histology in F2-F3 MASH, SYNCHRONY Outcomes in F4 compensated cirrhosis, and SYNCHRONY Real-World in non-invasively diagnosed MASH/MASLD, whose double-blind portion completed enrollment with safety results expected in 2026).

Efinopegdutide (MK-6024, formerly HM12525A and JNJ-64565111) is an investigational once-weekly subcutaneous dual agonist of the GLP-1 and glucagon receptors being developed by Merck for metabolic dysfunction-associated steatohepatitis (MASH, formerly NASH) and steatotic liver disease. It is a synthetic oxyntomodulin-based peptide - a modified GLP-1/glucagon dual-agonist sequence conjugated to a human IgG4 Fc fragment through a 10 kDa polyethylene glycol linker using Hanmi Pharmaceutical's LAPSCovery half-life-extension platform, which stretches dosing to once weekly. The design pairs the GLP-1 arm (appetite suppression, glycemic control, weight loss) with a glucagon arm that raises energy expenditure and acts directly on the liver to burn hepatic fat - the feature that sets it apart from pure GLP-1 drugs. In the head-to-head Phase 2a trial in NAFLD (Journal of Hepatology, 2023), efinopegdutide 10 mg cut liver fat content by 72.7% at 24 weeks versus 42.3% for semaglutide 1 mg, with two-thirds of efinopegdutide recipients falling below the 5% liver-fat threshold that defines a normal liver. Merck holds FDA Fast Track designation for the MASH program and is running Phase 2b studies plus a dedicated trial in compensated cirrhosis due to steatohepatitis; the earlier type 2 diabetes and obesity indications were discontinued in favor of the liver focus.