Domagrozumab
Muscle Growth & Body CompositionAlso known as: PF-06252616, RG7888
Mechanism
Domagrozumab is a humanized anti-myostatin antibody developed by Pfizer for Duchenne muscular dystrophy (DMD). It showed promise in preclinical models by increasing muscle mass in dystrophin-deficient mice, but Phase 2 results in DMD boys were disappointing, failing to improve the primary functional endpoint. Development was discontinued for DMD.
Technical detail
Domagrozumab (PF-06252616) is a humanized IgG1 monoclonal antibody targeting myostatin (GDF-8) with high affinity and selectivity. In mdx mouse models of DMD, it produced significant increases in muscle mass and grip strength. However, the Phase 2 HEIDIS trial in ambulatory DMD patients (ages 6-15) failed to demonstrate improvement in the 4-stair climb primary endpoint versus placebo after 48 weeks, despite showing trends toward increased lean body mass. Development for DMD was discontinued in 2018. The failure highlighted that increasing muscle mass alone may be insufficient in dystrophic muscle lacking functional dystrophin.