SMA therapy apitegromab could be available by end of year, if approved
Decision by FDA due in September; EU also reviewing application
Scholar Rock plans to have the the muscle-strengthening therapy apitegromab available commercially in the U.S. before the end of the year if the U.S. Food and Drug Administration (FDA) approves it next month as an add-on treatment for spinal muscular atrophy (SMA).
The company sought the agency’s approval this year and a decision is expected by Sept. 22. An application for SMA is also being reviewed in the European Union. Scholar Rock said it hopes to launch apitegromab in Europe in 2026 if it wins approval.
Apitegromab’s applications are based mainly on findings from a Phase 3 clinical trial called SAPPHIRE (NCT05156320), the results of which were recently published in The Lancet Neurology, in a study titled, “Safety and efficacy of apitegromab in nonambulatory type 2 or type 3 spinal muscular atrophy (SAPPHIRE): a phase 3, double-blind, randomised, placebo-controlled trial.” The study was funded by Scholar Rock.
“The SAPPHIRE findings support the value of muscle-targeted therapies for children and adults living with SMA,” Akshay Vaishnaw, MD, PhD, president of research and development at Scholar Rock, said in a company press release.
SMA is chiefly caused by mutations that lead to reduced levels of the SMN protein. As a result, the nerve cells that control movement, called motor neurons, sicken and die, leading to muscle weakness and wasting.
Several disease-modifying therapies for SMA boost the protein’s levels. SMN-targeting treatments can help slow the disease’s progression, but addressing the progressive muscle weakness that leads to the loss of motor function remains an unmet need.
How does apitegromab work in SMA?
Apitegromab was developed as an add-on to disease-modifying therapy to help boost muscle strength by blocking myostatin, a protein that normally limits muscle growth.
“The robust apitegromab data reinforce that effective SMA treatment regimens should address both motor neuron preservation and muscle function,” Vaishnaw said. “To improve outcomes and support activities like breathing, eating, swallowing, standing and walking, which require muscle strength and motor function, a comprehensive approach targeting both components of the disease is critical.”
SAPPHIRE enrolled 188 children and young adults with SMA type 2 or type 3 who were taking the SMN-targeting medicines Spinraza (nusinersen) or Evrysdi (risdiplam). All the participants were able to sit independently and the researchers noted its demographics were “broadly representative of the [SMA] population.” While the study enrolled only people with certain types of SMA, the results “could be broadly applicable to all people living with [SMA],” they said.
The participants were randomly assigned to take apitegromab or a placebo every four weeks for a year. The therapy was given by infusion into the bloodstream; each one taking about two hours at first, but this was able to be sped up to an hour if it was well tolerated. Two doses were tested in younger children, though the results with both were comparable.
The study met its main goal of demonstrating that apitegromab led to more extensive improvements on the Hammersmith Functional Motor Scale Expanded (HFMSE), a standard measure of motor function. Average HFMSE scores at its end were 1.8 points better with apitegromab than the placebo. This difference represents “statistically significant and potentially clinically meaningful improvements in motor function,” said the researchers, who noted that increased HFMSE scores in patients given apitegromab were detectable eight weeks into treatment.
Scores on the Revised Upper Limb Module (RULM), a measure of arm and hand function, also tended to improve more with apitegromab than the placebo. This result wasn’t statistically significant, however, meaning the difference could be due to random chance. RULM scores tended to change more slowly than HFMSE scores, the researchers noted.
SAPPHIRE safety data were generally consistent with the known clinical profile of SMA patients taking SMN-targeting therapies. Adverse events at least 5% more common among those taking apitegromab included vomiting, inflammation of the stomach and intestines (gastroenteritis), diarrhea, runny nose, and pneumonia. No serious side effects were reported.
“Overall, SAPPHIRE showed that apitegromab improved motor function and was generally well tolerated, supporting the use of muscle-targeting therapy for individuals with spinal muscular atrophy,” the researchers wrote.
About the Author
