Domagrozumab (PF-06252616)
Domagrozumab (PF-06252616) is a humanised anti-myostatin monoclonal antibody developed for Duchenne muscular dystrophy. Despite increasing muscle volume on MRI in a Phase 2 trial, it failed to meet its primary functional endpoint (4-stair climb time), and the programme was discontinued.
01 Overview
Domagrozumab binds myostatin to block its suppression of muscle growth. In a Phase 2 study in ambulatory boys with DMD, treatment produced measurable increases in muscle volume and some early functional signals versus placebo.
However, at the end of the placebo-controlled period the drug did not achieve a statistically significant improvement on the primary functional outcome, and Pfizer ended development. Like stamulumab, it reinforced that myostatin inhibition can grow muscle imaging metrics without reliably improving patient function.
02 Mechanism
A humanised IgG1 monoclonal antibody that neutralises mature myostatin, preventing ActRIIB activation and de-repressing muscle protein synthesis.
03 Dosing
| Tier | Dose | Route | Notes |
|---|---|---|---|
| Trial dosing (DMD) | 5–40 mg/kg/wk | IV | Given roughly every 4 weeks in Phase 2; not marketed. |
04 Effects
| Effect | Magnitude | Evidence | |
|---|---|---|---|
| Increased muscle volumeMRI showed greater thigh muscle volume in treated boys versus placebo. | Measurable on MRI | Clinical | |
| Functional improvementThe primary 4-stair-climb functional endpoint was not met. | Not significant | Clinical |
05 Side effects
| Effect | Severity | Frequency | Evidence | Countermeasures |
|---|---|---|---|---|
| Injection/infusion reactionsInfusion-associated reactions were among the adverse events reported. | Mild | Common | Clinical | |
| Falls and musculoskeletal eventsCommon childhood musculoskeletal events (falls, contusions) were reported across arms in the paediatric trial. | Moderate | Common | Clinical |