Pegbelfermin

Summary

Pegbelfermin (BMS-986036) is a PEGylated FGF21 analogue developed by Bristol Myers Squibb for the treatment of nonalcoholic steatohepatitis (NASH) and primary biliary cholangitis (PBC). It targets metabolic pathways to reduce liver fat, inflammation, and fibrosis. Phase 2 trials showed promising reductions in hepatic fat and fibrosis markers, though broader Phase 3 development has faced challenges.

Mechanism of Action

Pegbelfermin is a PEGylated analogue of fibroblast growth factor 21 (FGF21) that activates FGF21 receptors (FGFR1c/β-klotho complex), modulating lipid metabolism, reducing hepatic lipogenesis, improving insulin sensitivity, and decreasing hepatic steatosis and fibrosis.

Routes of Administration

Goals & Uses

• Treatment of primary biliary cholangitis (PBC)Liver DiseaseLow
• Reduction of hepatic fibrosis in NASHLiver DiseaseModerate
• Improvement of dyslipidemiaMetabolicModerate
• Improvement of insulin sensitivityMetabolicLow
• Reduction of hepatic steatosis in NASHMetabolic / HepatologyModerate

Contraindications

• PregnancyPopulationHighPotential fetal risk or insufficient safety data
• Known hypersensitivity to pegbelfermin or PEG-containing productsAllergyHigh

Adverse Effects

• Injection site reactionsLocalCommon
• AlopeciaDermatologicUncommonHair loss
• HeadacheNeurologicUncommonPain in the head or upper neck
• NauseaGastrointestinalCommonFeeling of sickness or urge to vomit
• Anti-drug antibodies (ADA)ImmunologicalUncommon
• DiarrheaGastrointestinalUncommonLoose or frequent stools

Drug Interactions

• Insulin / insulin secretagoguesModerate
• Lipid-lowering agents (statins, fibrates)Low

Population Constraints

• Severe renal impairmentOrgan ImpairmentRelative
• Pediatric patientsAgeRelative
• Lactating womenReproductiveRelative
• Severe hepatic impairment (Child-Pugh C)Organ ImpairmentRelative

Regulatory Status

• European UnionInvestigationalNo marketing authorization; participated in European clinical trial sites.
• United StatesInvestigationalInvestigated under IND; Phase 2 trials completed for NASH (FALCON 1/2). No NDA filed as of last available data.
• United KingdomInvestigationalNo MHRA approval; investigational use only in clinical trials.

Not approved by FDA, EMA, or other major regulatory agencies. Investigated under IND in Phase 2 clinical trials for NASH and PBC. Development status uncertain after mixed Phase 2 results and pipeline re-evaluations.

Evidence & Sources

No sources recorded yet.