Bimagrumab (BYM338)
Bimagrumab (BYM338) is a fully human monoclonal antibody that blocks activin type II receptors (ActRIIA/B), the shared receptors for myostatin and activin. Originally tested in muscle-wasting conditions, it gained attention when trials in obesity and type 2 diabetes showed simultaneous loss of fat mass and gain in lean mass.
01 Overview
Rather than neutralising myostatin, bimagrumab binds the ActRII receptors themselves, blocking myostatin, activin and related ligands at the cell surface. In sarcopenia and inclusion body myositis, muscle-mass gains were seen but functional benefit was inconsistent.
Interest surged when a Phase 2 study in adults with obesity and type 2 diabetes reported roughly 20% reduction in fat mass alongside an increase in lean mass over 48 weeks — a body-composition profile distinct from diet or incretin drugs. This repositioned bimagrumab as a potential obesity and body-composition agent, including in combination with GLP-1 therapies.
02 Mechanism
A fully human IgG1 monoclonal antibody that binds activin type II receptors (ActRIIA and ActRIIB), competitively blocking myostatin and activin signalling to increase muscle mass and reduce fat mass.
03 Dosing
| Tier | Dose | Route | Notes |
|---|---|---|---|
| Trial dosing (obesity/T2D) | 10–30 mg/kg | IV | Given roughly every 4 weeks in the Phase 2 obesity/diabetes trial; not marketed. |
04 Effects
| Effect | Magnitude | Evidence | |
|---|---|---|---|
| Fat mass reductionObesity/T2D trial showed a large reduction in total body fat mass versus placebo. | ~20% at 48 weeks | Clinical | |
| Increased lean massLean mass rose while fat fell, a favourable body-composition shift. | ~2-3% gain | Clinical | |
| Improved glycaemic controlHbA1c improved in the diabetic cohort. | HbA1c reduction | Clinical |
05 Side effects
| Effect | Severity | Frequency | Evidence | Countermeasures |
|---|---|---|---|---|
| Mild diarrhoeaGI upset including diarrhoea was reported more often than placebo. | Mild | Common | Clinical | |
| Muscle cramps / spasmsMuscle spasms and cramps were among the most frequent adverse events. | Mild | Common | Clinical | |
| Pancreatic enzyme / lipase elevationTransient increases in pancreatic enzymes were observed in some participants. | Moderate | Uncommon | Clinical |