Pfizer takes muscular dystrophy drug into phase II

Pfizer has started phase II trials of a candidate drug to treat Duchenne muscular dystrophy (DMD) as it plays catch-up with rivals PTC Therapeutics, Prosensa and Sarepta.

The pharma giant has started enrolling patients into the trial of PF-06252616, a monoclonal antibody targeting the protein myostatin which is involved in the regulation of skeletal muscle growth.

DMD is a disease which afflicts boys and is characterised by severe muscle-wasting that generally leads to death before the age of 30. For a number of years it has been suggested that inhibiting myostatin could be a treatment for degenerative muscle diseases such as DMD, although experimental evidence has been conflicting.

Almost a decade ago experiments to knock out the gene coding for myostatin in mice engineered to mimic DMD suggested that, while the approach increased muscle formation, it reduced fat formation and did not reduce muscle pathology or mortality.

A few years later, a clinical trial of a myostatin inhibitor called stamulumab (MYO-029) developed by Wyeth (which was acquired by Pfizer in 2009) showed some promise in early trials but was subsequently abandoned after additional analyses found no improvements in muscle strength or function, and no statistically significant muscle growth in trial participants.

PF-0625616 is a follow-up to the stamulumab programme and will be tested in boys aged six to 10 years old diagnosed with DMD, regardless of genotype.

Its mechanism is markedly different from other DMD therapies on or nearing the market, which are designed to restore the function of a protein – called dystrophin – that is impaired in DMD.

PTC Therapeutics’ small-molecule drug Translarna (ataluren) is already on the market in Europe and addresses ‘nonsense’ mutations in DMD. Meanwhile, drisapersen from Prosensa – in the process of being acquired for $840 million by BioMarin – as well as Sarepta’s eteplirsen ‘exon-skipping’ therapies that can lead to partial restoration of dystrophin function and are both in late-stage development.

“We are enthusiastic about the potential for myostatin inhibitors to stimulate increases in muscle mass and strength for people living with DMD,” commented Sharon Hesterlee, vice president of Research for Parent Project Muscular Dystrophy (PPMD).

“This approach could potentially add an important angle in our fight against this disease and we are pleased to see the time and great care that Pfizer has expended on its development,” she added.


Prosensa begins submission of Duchenne’s drug to FDA

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