Roche, citing discouraging clinical trial results, has chosen to stop developing an experimental antibody drug as a potential treatment for two rare, muscle-wasting diseases.
Known as emugrobart, the drug is meant to lower levels of a protein, “myostatin,” that both breaks down muscle fibers and restricts new muscle from building. Chugai Pharmaceutical, a Japan-based Roche subsidiary, designed it to bind to, and thereby keep inactive, a precursor protein to myostatin. Researchers have been testing emugrobart against spinal muscular atrophy and facioscapulohumeral muscular dystrophy, and as a way to retain lean muscle mass in people with obesity who are taking a GLP-1 medication.
In SMA, Roche has been sponsoring a two-part trial to evaluate whether it’s worth adding emugrobart on top of the company’s already approved therapy Evrysdi. The experiment aimed to recruit around 250 patients, and focused on safety as well as biological markers of muscle health.
But, after a “comprehensive assessment” of all the evidence gathered in the first part of the experiment, the Swiss pharmaceutical giant determined its drug “did not consistently deliver” enough improvements in muscle growth and motor function to warrant further study.
“We recognise this news will be disappointing to the SMA community,” wrote Louisa Townson, Roche’s patient partnership director for rare diseases, in a Thursday letter to a European patient advocacy group, explaining the company’s decision.
Townson added that Roche “remains committed to advancing quality care for people living with SMA,” and plans to share data from the trial at an upcoming medical conference “so that this research can also help to inform the development of future treatments.” She penned a similar letter to the facioscapulohumeral muscular dystrophy community, referring to a separate mid-stage trial that also generated less-than-ideal results.
While estimates vary, the number of people living with SMA in the U.S. is generally thought to be in the range of 10,000 to around 30,000. It mostly affects young children, and is caused by alterations in a gene responsible for making “survival motor neuron,” a protein crucial for signaling between muscles and the nervous system.
While historically fatal, the prognosis for this disease changed drastically over the past decade as three medicines — Biogen’s antisense drug Spinraza, Novartis’ gene therapy Zolgensma and Evrysdi — became available to patients. Each of these works by boosting survival motor neuron levels.
Last year, sales of Evrysdi, which is taken orally, totaled 1.76 billion Swiss francs, or roughly $2.1 billion. Roche had been hoping to expand the business with emugrobart, which, by targeting myostatin, offered a different route to addressing SMA. It’s a strategy adopted by other developers as well, including Biohaven and Massachusetts-based Scholar Rock.
Eric Schmidt, an analyst at Cantor Fitzgerald who covers Scholar Rock, highlighted how its drug apitegromab has been ahead of Roche’s for several years, and is now being developed as both an under-the-skin shot along with a monthly intravenous infusion. Roche, therefore, “offered little in the way of differentiation,” according to Schmidt.
“We now expect apitegromab to have near complete market share as the lone muscle-building therapy for SMA patients,” the analyst wrote in a Thursday note to clients, adding that his team sees an approval from the Food and Drug Administration this year as a "when not if" event. The Cantor team expects the therapy, which the FDA rejected last year due to manufacturing concerns, to have multibillion-dollar potential.
Roche’s update is a “clear win” for Scholar Rock ahead of a “likely FDA approval,” wrote Raymond James analyst Martin Auster in his own note to clients.
Shares of Scholar Rock were up 1.5%, to a little over $46 apiece, in late morning trading Friday. Biohaven shares were up 2.5%.
