Drug Development

Pfizer axes a key Duchenne MD program after PhII flop, raising new doubts for a drug category that attracted Roche and Biogen

Pfizer is jettisoning another disappointing drug that’s been in the clinic for Duchenne muscular dystrophy. The pharma giant says it’s axing work on domagrozumab (PF-06252616) — raising the odds against one R&D focus in the field that has attracted some marquee players around the world.

The drug is one of several designed to inhibit myostatin, which flopped against a one-year test of muscle strength, failing to help patients to any significant degree. By suppressing myostatin, which blunts muscles, the theory is that a proper therapy can help slow the muscle-wasting ailment that inevitably proves fatal to the boys who inherit this disease.

Seng Cheng

The failure eliminates one of several anti-myostatin therapies, including BMS-986089, a drug which Bristol-Myers sold to Roche in the spring of 2017 for $170 million in cash and $205 million in milestones. That drug — now called RG6206 (RO7239361) — is in a Phase II/III study.

Just a month ago Biogen also got into the myostatin game, paying $27 million in cash to grab a Phase Ia drug called ALG-801 (BIIB110) and a preclinical drug ALG-802 from AliveGen. Biogen noted at the time that the two drugs “represent novel ways of targeting the myostatin pathway, which is one of the most thoroughly studied approaches for muscle enhancement.” These therapies are designed to target the nystatin pathway, which Biogen believes could work better than other drugs in the clinic.

There’s nothing unusual about failure in this field, though, where Duchenne MD has proven a tough objective. Novartis experienced a late-stage setback with their myostatin drug bimagrumab (BYM338) in 2016. Atara–an Amgen ($AMGN) spinoff–saw its clinical candidate PINTA 745 fail a Phase II study for protein energy wasting in patients with end-stage renal disease, forcing the biotech to halt development efforts and switch focus to cancer. Back in 2011, Acceleron ($XLRN) and Shire ($SHPG) also halted clinical work on ACE-031, another myostatin drug with big dreams in fighting muscle wasting, then decided to scrap it altogether in 2013 after running some additional preclinical tests.

It’s just as bad in other related muscle drug fields. Two months ago shares of Summit were crushed in the wake of their failed Phase II for a utrophin modulator, ezutromid.

Duchenne MD has also been a mine field of controversy in R&D. Sarepta gained an approval for eteplirsen, without convincing regulators it actually works. Now the biotech has been shifting attention to its gene therapy — put on hold recently due to impurities found in a third-party provided plasmid — which has looked promising at the very earliest stages of tracking patient responses. PTC, meanwhile, has been pursuing an FDA OK for ataluren, approved in Europe despite repeated failures in the clinic. 

Not to be overlooked is Scholar Rock, where the executive team believes they can find success by targeting latent rather than active myostatin. The biotech, though, felt the heat Thursday morning, with its shares plunging 12% on the news. That setback triggered a flurry of defensive posts from analysts defending Scholar Rock and burnishing their chances, with one less rival to worry about.

Pfizer hasn’t quite given up on its drug, leaving the door open to future trials in muscular diseases. But its big remaining effort in DMD is in a gene therapy program it has underway for PF-06939926, an AAV delivered treatment which carries a shortened version of the human dystrophin gene (mini-dystrophin).

“We are disappointed by these results and while we are not progressing with the studies, the data will contribute to a greater understanding of this disease and we will evaluate the total data set to see if there is a place for this medicine in muscular diseases,” said Seng Cheng, the CSO for the Pfizer Rare Disease Research Unit.

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