Pegozafermin

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

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.

The first dual GCG/GLP-1 receptor agonist approved in China for obesity and T2D, with Phase 3 showing up to 20.1% weight loss at the 9 mg dose and superiority over semaglutide.

A GLP-1/glucagon dual receptor agonist with FDA Breakthrough Therapy Designation for MASH, showing strong weight loss and liver benefits in Phase 2 trials.

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.

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).

Efimosfermin alfa (development code BOS-580) is an investigational, long-acting, engineered analog of the metabolic hormone fibroblast growth factor 21 (FGF21) being developed by GSK - which acquired the molecule from Boston Pharmaceuticals in May 2025 for $1.2 billion upfront and up to $800 million in milestones (potential ~$2 billion total) - for steatotic liver disease, principally metabolic dysfunction-associated steatohepatitis (MASH, formerly NASH). Its defining feature is a very long half-life engineered to allow once-monthly subcutaneous dosing - the least frequent schedule among the leading FGF21 analogs, contrasting with the once-weekly or every-two-weeks dosing of efruxifermin (an Fc-FGF21 fusion) and pegozafermin (a glycoPEGylated FGF21). Like the rest of the class, it activates FGF receptors (FGFR1c/2c/3c) together with the co-receptor beta-Klotho to cut liver fat, improve insulin sensitivity, lower triglycerides, and drive direct anti-inflammatory and anti-fibrotic effects in the liver. In a 24-week Phase 2 trial in biopsy-confirmed F2-F3 MASH, once-monthly efimosfermin achieved at least one-stage fibrosis improvement without worsening of MASH in about 45% of patients and MASH resolution without worsening of fibrosis in about 68%, both significantly better than placebo (published in The Lancet, 2025). It holds FDA Breakthrough Therapy designation and EMA PRIME (Priority Medicines) status for MASH, and has advanced into the Phase 3 ZENITH program (ZENITH-1 and ZENITH-2 in F2-F3 MASH), with a Phase 3 program in compensated (F4) MASH cirrhosis also underway; GSK has guided to a first potential launch around 2029.