Domagrozumab (PF-06252616) is an investigational drug, being developed by Pfizer, that is currently in a Phase 2 clinical trial evaluating its efficacy in treating Duchenne muscular dystrophy (DMD),  a genetic disorder characterized by muscle tissue loss and weakness.

Mechanism of Action 

Domagrozumab is a monoclonal anti-myostatin antibody, which is an engineered protein that binds to myostatin and blocks 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 don’t grow too large. So a therapy that inhibits myostatin may improve muscle function in people with a muscle wasting disease by allowing for greater muscle growth.

The protein is active both before and after birth.

Clinical studies of domagrozumab

Pfizer is exploring the potential of domagrozumab to increase muscle mass and function in DMD patients in a Phase 2 clinical trial (NCT02310763) that is currently recruiting across the U.S., Australia, Canada, Japan, and Europe (the U.K., Italy, Poland, and Bulgaria). Participants, boys ages 6–15, must have confirmed DMD, be ambulatory and able to climb four stairs (with or without the use of handrails) in a set time, and be taking glucocorticosteriods for at least six months prior to the study’s start.

The randomized, double-blind, and placebo-controlled trial aims to determine the drug’s safety, tolerability, efficacy, pharmacokinetics (what the body does to a drug), and pharmacodynamics (what a drug does to the body). It  consists of two periods, each of 48 weeks. About 105 boys will be divided into three groups: the first will receive domagrozumab  in period 1 and remain on a stable dose in period 2; the second will receive the drug in period 1 but switch to placebo in period 2; and the third will receive placebo in period 1 then switch to the treatment in period 2.

Patients will be given monthly intravenous doses of the drug at three doses —  5mg/kg, 20 mg/kg and 40 mg/kg — or placebo. All will undergo regular clinical examinations and blood tests to ensure safety. This study’s primary goal is the drug’s tolerability at different doses, and measured changes from baseline (study start) in the four-stair climb compared to placebo.

To study domagrozumab’s effective, functional evaluations like the stair climb and the six minute walk distance will be tested every two months, and the leg muscles will be evaluated three times per year by MRI (magnetic resonance imaging) scans.

Pfizer reports the study has met the two-thirds milestone, with the drug being well-tolerated with no adverse effects. The study is expected to finish in August 2019.

An open-label extension study (NCT02907619), evaluating domagrozumab’s long-term safety and efficacy, is also underway.  Boys who complete the Phase 2 study will 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, Pfizer reported, and the study itself is set to conclude in March 2021.