Domagrozumab (PF-06252616)

Domagrozumab (PF-06252616) was an investigational treatment being developed by Pfizer for Duchenne muscular dystrophy (DMD), a genetic disorder characterized by muscle tissue loss and weakness. Investigation into the treatment was terminated in August 2018 after a Phase 2 clinical trial failed to meet its primary endpoint.

How domagrozumab works

Domagrozumab is a monoclonal anti-myostatin antibody, which is an engineered protein that can bind to myostatin and block its activity.

Myostatin, encoded by the MSTN gene, is a muscle protein — found largely in muscles that control movement (skeletal muscles) — that restrains muscle growth to ensure they do not grow too large. So a therapy that inhibits myostatin may improve muscle function in people with muscle-wasting conditions by allowing for greater muscle growth.

Domagrozumab in clinical trials

Domagrozumab was first tested in a Phase 1 clinical trial (NCT01616277) involving healthy volunteers. Completed in 2014, the trial enrolled 86 participants and showed that the treatment was well-tolerated with no severe adverse events. The results were published in 2018 with the most common side effects being headaches, respiratory tract infections, muscle spasms, and fatigue.

Pfizer then initiated a Phase 2 clinical trial (NCT02310763) to explore the potential of domagrozumab in increasing muscle mass and function in DMD patients. The trial enrolled boys, from 6 to 15 years old, with confirmed DMD and still able to walk and climb at least four stairs with or without the use of handrails in a set time, and who were taking corticosteroids for at least six months prior to the study’s start.

The randomized, double-blind, and placebo-controlled trial investigated the treatment’s safety, tolerability, efficacy, pharmacokinetics (movement in the body), and pharmacodynamics (effect on the body). It consisted of two periods, each lasting 48 weeks.

A total of 121 boys were divided into three groups: the first received domagrozumab in period 1 and remained on a stable dose in period 2, the second received the treatment in period 1 but switched to a placebo in period 2, and the third received a placebo in period 1 then switch to the treatment in period 2.

Patients were given monthly intravenous doses of the treatment at three doses: 5 mg, 20 mg, or 40 mg per kg of body weight, or a placebo. All patients underwent regular clinical examinations and blood tests to ensure that the treatment was safe. This study’s primary goal was the treatment’s tolerability at different doses, and measured changes from baseline (study start) in the four-stair climb compared with a placebo.

To study domagrozumab’s effectiveness, functional evaluations such as the stair climb and the six-minute walk distance were performed every two months, and leg muscles were evaluated three times per year by magnetic resonance imaging (MRI) scans.

Pfizer announced, in August 2018, that the study did not meet the primary efficacy endpoint showing any significant difference between the treatment groups and placebo groups in the four-stair climb test, and that domagrozumab’s development would be terminated.

An open-label extension study (NCT02907619), evaluating domagrozumab’s long-term safety and efficacy, was also underway. Boys who completed the Phase 2 study were to be enrolled and given monthly injections of the maximum dose they tolerated in the earlier trial. The first patient entered the extension study in October 2016. With the failure of the Phase 2 trial, this open-label extension was also terminated.


Last updated: Jul. 10, 2019


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