Another myostatin program combusts, but Acceleron has plenty in the pipeline
Myostatin inhibitors — engineered to build muscle and improve mobility in patients — theoretically make sense for use in patients with muscle-wasting diseases. But the field is littered with failure — and so it was hardly surprising when Acceleron, which years ago scrapped a myostatin program it had partnered with Shire, disclosed another flopped myostatin drug on Monday.
Acceleron’s drug, ACE-083, was being tested in a mid-stage study in patients with Charcot-Marie-Tooth disease (CMT), a group of inherited disorders that cause nerve damage and are characterized by smaller, weaker muscles.
In the study, ACE-083 induced a statistically significant increase in mean total muscle volume — meeting the main goal. However, that increase did not translate to statistically significant improvements in any of the functional or quality of life secondary endpoints, versus placebo. Acceleron is, therefore, discontinuing the development of the experimental compound, it said.
Back in September, ACE-083 failed to elicit functional benefit in a separate study in patients with facioscapulohumeral muscular dystrophy, a genetic muscle-wasting condition that causes the muscles of the limbs, shoulders, and face to weaken.
This CMT result was not surprising, given the similar lack of functional benefit from the FSHD trial, SVB Leerink’s Geoffrey Porges wrote in a note.
The Cambridge, Massachusetts-based company’s stock $XLRN closed down about 6.6% at $85.29 on Monday and was barely down 0.1% in Tuesday premarket trading.
ACE-083 is the latest casualty in a list of myostatin efforts that have crashed and burned. Acceleron and Shire halted clinical work on ACE-031 as early as 2011 and scrapped the program altogether in 2013; Novartis’ bimagrumab failed a mid-stage study in 2016; Pfizer dropped the Duchenne plans for domagrozumab following a disappointing Phase II trial in 2018; and last November, Roche abandoned its Duchenne drug (acquired from Bristol Myers Squibb in 2017) after a futility analysis suggested developing the compound further was futile.
Myostatin is a protein that forms part of the transforming growth factor beta (TGFβ) superfamily — a group of proteins that help control the growth and development of tissues across the body. The protein normally restrains muscle growth, ensuring that muscles do not grow too large.
Meanwhile, Acceleron has other areas of focus.
The company in November secured the approval of Celgene-partnered red blood cell boosting drug Reblozyl — known chemically as luspatercept — to treat anemia in patients with beta-thalassemia who require regular transfusions. Although its use in myelodysplastic syndromes — which will likely determine if the drug, pegged to eventually generate global peak sales of more than $3 billion, is a big commercial success — is still under Phase III review.
Earlier this year, focus also turned to sotatercept as the company reported positive mid-stage data in patients with pulmonary arterial hypertension (PAH). Unlike existing PAH therapies that are designed to dilate the pulmonary arteries and reduce blood pressure, sotatercept is engineered to restore BMPR-II signaling, a key driver of the disease. If all goes well in pivotal studies, and the drug wins approval — Porges estimates the drug could rake in global sales of about $1.2 billion in 2028.
“After that (FSHD) result we removed all of the value of this program from our model and forecasts, and for this reason, this (CMT) disclosure has no impact on our valuation,” Porges said.
“It does confirm that Acceleron investors and management were indeed fortunate that their sotatercept phase II trial in PAH had a positive outcome, and the magnitude of the benefit in that trial, and the future development path, timeline and cost, become even more important to the stock and its value now.”