RESEARCH MONOGRAPH · KDC-MN-361

Domagrozumab

May 9, 2026 Kodiac biolabs Research Revised May 30, 2026 2 min read

Our opinion on this compound

52/100

Pfizer's anti-myostatin antibody, killed by a DMD trial miss after the muscle volume gains didn't translate

Domagrozumab (PF-06252616) was Pfizer's swing at anti-myostatin therapy for Duchenne muscular dystrophy, and like most of the antibody-only myostatin neutralizers, the mechanism story was clean but the clinical translation didn't quite land.

The pharmacology was a humanized IgG1 antibody binding mature myostatin with high affinity, designed to spare the activin and BMP ligands that broader receptor-level approaches (ACE-031, bimagrumab) also affect. The pre-clinical data in mdx mice and other dystrophy models showed expected muscle hypertrophy effects, and the phase 1/2 trial showed muscle volume increases on MRI in DMD boys.

The phase 3 trial (NCT02310763) hit its key efficacy issue: the primary endpoint of 4-stair climb time at one year didn't separate from placebo, despite the muscle volume gains. Pfizer terminated development in 2018. The same pattern that killed MYO-029 a decade earlier replayed in a more rigorous trial: you can make dystrophic muscle bigger, but bigger doesnt necessarily mean functionally stronger when the underlying dystrophin deficiency is still driving muscle damage.

What's worth thinking about from this and similar failures is whether the dystrophy populations were ever the right efficacy population. The myostatin pathway is a brake on healthy muscle growth, and removing the brake in tissue that's structurally compromised may produce hypertrophy in the surviving fibers without solving the regeneration-and-damage cycle. Cachexia, sarcopenia, and obesity-related muscle loss may be better-suited populations because the underlying muscle is intact. The bimagrumab data in T2D obesity supports that read.

Sourcing as a research antibody is essentially closed. Domagrozumab is Pfizer proprietary, and the research-grade alternatives for studying myostatin neutralization in vivo are different reagents.

For research, domagrozumab is mostly historical and serves as evidence that anti-myostatin antibody approaches can reliably produce hypertrophy in humans but that the indication selection matters enormously. The DMD trial outcomes don't tell you the pathway is wrong, they tell you the patient population was probably wrong for this specific drug.

The next generation of myostatin pathway interventions (ApitBatRumab, follistatin analogs, more recent activin receptor traps) is honestly more interesting as a current research direction.

Evidence: 50
Mechanism: 75
Reliability: 55
Safety: 75
Sourcing: 35
Value: 35
Signal: 50
Staying power: 40

Plain-language summary Intrigue 50 / 100

Domagrozumab (PF-06252616) is Pfizer's second-generation anti-myostatin antibody, designed for higher affinity than stamulumab. The pivotal phase 2 trial in Duchenne muscular dystrophy (2018) showed meaningful muscle mass increases on MRI but failed to demonstrate functional benefit on the primary motor outcome, leading Pfizer to terminate the program. The pattern (muscle mass without function) has now repeated across nearly every anti-myostatin compound tested in muscular dystrophy and is the central puzzle of the field: blocking myostatin reliably grows muscle but does not seem to make patients meaningfully stronger. Not stocked by Kodiac. This monograph is provided for research and educational reference.

Intrigue 0–100 blends mechanism novelty, evidence strength, and translational potential. Kodiac editorial, not peer-reviewed.

Anti-myostatin monoclonal antibody

A humanized anti-myostatin monoclonal antibody developed at Pfizer for Duchenne muscular dystrophy; phase 2 trial failed.

Abstract

Domagrozumab (PF-06252616; humanized IgG1 monoclonal antibody; molecular weight approximately 145 kDa) is a humanized anti-myostatin monoclonal antibody developed at Pfizer. The compound is selective for myostatin (GDF-8) with high affinity, designed to neutralize circulating myostatin in Duchenne muscular dystrophy. Phase 2 trial in DMD (2018) demonstrated muscle mass increases on MRI but no significant improvement in functional endpoints (6-minute walk test, North Star Ambulatory Assessment); Pfizer discontinued development. The trial result reinforced a broader concern about myostatin inhibition in DMD: muscle mass gains may not translate to clinical benefit if the underlying dystrophin deficiency continues to cause fiber damage. Used as a research compound for selective myostatin neutralization in DMD context.

Mechanism of action

Humanized monoclonal antibody against myostatin; selective neutralization of GDF-8.

Reported research dose ranges

Trial doses 5 to 40 mg/kg intravenous every 4 weeks.

References

Wagner KR, et al. A phase 2 placebo-controlled trial of domagrozumab in patients with Duchenne muscular dystrophy. Neurology 2020.
St. Andre M, et al. A mouse anti-myostatin antibody increases muscle mass and improves muscle strength. Skeletal Muscle 2017.
Bhattacharya I, et al. Pharmacokinetics and pharmacodynamics of domagrozumab. J Clin Pharmacol 2018.

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KDC-MN-361

The full reference document is provided strictly for research use only. It reports research dose ranges from the published literature, not instructions for use in humans or animals.

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FOR RESEARCH USE ONLY. Not for medical, diagnostic, or therapeutic purposes. Not for human consumption. All information is provided for research and educational purposes only.

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Domagrozumab

Abstract

Mechanism of action

Reported research dose ranges

References

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Abstract

Mechanism of action

Reported research dose ranges

References

Read the full monograph

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