Pfizer has halted development of its Duchenne muscular dystrophy (DMD) candidate domagrozumab on disappointing results in a mid-stage efficacy trial.
The big pharma company halted two trials of the anti-myostatin antibody, which is designed to build muscle mass and strength. Myostatin is a muscle protein that restrains muscle growth to ensure they don’t grow too large, and it has been hypothesised that blocking it could help offset the muscle-wasting that occurs in DMD.
Domagrozumab (PF-06252616) was unable to achieve an improvement in a stair-climbing test compared to placebo in the phase II trial, which included a full year of treatment with the antibody. While it’s too early to tell, the lack of efficacy might relate to lab experiments which suggest that while blocking myostatin can increase muscle mass, the larger muscles aren’t functionally stronger.
Pfizer will keep evaluating the trial data “to see if there is a place for this medicine in muscular diseases,” according to Seng Cheng, senior vice president and chief scientific officer, Pfizer Rare Disease Research Unit. The decision was not taken because of any safety issues with the drug, he stressed.
News of the setback spurred modest gains in the share price of Sarepta, which sells exon-skipping therapy Exondys 51 (eteplirsen) in the US and Europe, as well as PTC Therapeutics which markets Translarna (ataluren) in Europe.
At the moment these are the only two drugs available to treat the underlying dystrophin gene mutation in some DMD patients, although Marathon Pharma won US approval for a novel steroid to treat the symptoms of DMD – called Emflaza (deflazacort) – last year.
Pfizer still has an iron in the DMD fire, in the form of its Bamboo Therapeutics-developed gene therapy candidate PF-06939926. It is in a race to market with other gene therapies in clinical trials from Sarepta, Solid Biosciences and Genethon.
Pfizer started dosing patients with its mini-dystrophin candidate in March, and early data from the trial is due next year.
The failure of domagrozumab to move the needle in DMD could also give other companies developing myostatin-targeted therapies the jitters, including Biogen which has just agreed a $535m licensing deal with AliveGen for two myostatin inhibitor candidates. Biogen is however focusing initially on spinal muscular atrophy (SMA) and amyotrophic lateral sclerosis (ALS).
Meanwhile, Pfizer isn’t the first company to abandon a myostatin inhibitor for lack of efficacy. Novartis and Morphosys gave up on their bimagrumab for muscle-wasting disease sporadic inclusion body myositis two years ago, while Shire/Acceleron and Amgen have also chalked up failures in this category.