FDA denies apitegromab approval for SMA, cites manufacturing issues
Agency didn't note any issues related to safety, efficacy of proposed treatment
The U.S. Food and Drug Administration (FDA) has declined to approve apitegromab as a treatment for spinal muscular atrophy (SMA).
The FDA said it could not approve developer Scholar Rock‘s application at this time because of observations identified during a routine general site inspection of Catalent Indiana, a third-party fill-finish facility. This facility works on the final parts of manufacturing medical products, such as ensuring the product is sterilized.
According to Scholar Rock, the FDA’s observations were not specifically related to apitegromab, and the agency did not note any issues related to the safety or efficacy of the therapy, or with the drug product’s manufacturer.
Scholar Rock said Catalent has already submitted a response to the FDA to address the agency’s concerns. Once those issues are resolved, Scholar Rock plans to resubmit its application seeking approval of apitegromab. The company said it expects the agency to be able to quickly act on the application once the manufacturing issues are resolved.
“We are continuing to work closely with Catalent Indiana on the FDA’s manufacturing observations so that we can resubmit the apitegromab BLA [biologics license application] as soon as possible,” David L. Hallal, chairman and CEO of Scholar Rock, said in a company press release. “We remain focused on working [hand in hand] with the FDA to pursue approval of the first and only muscle-targeted treatment for people living with SMA.”
Adcocacy organization disappointed by apitegromab decision
Kenneth Hobby, president of Cure SMA, said the advocacy organization is “disappointed that the availability of a muscle-targeted treatment approach for patients with SMA has been delayed.” Nonetheless, Hobby and other advocates “remain enthusiastic about the transformative potential of apitegromab,” he added.
Scholar Rock has also applied to the European Union (EU) for approval of apitegromab. The EU application is still under review, and a decision is expected in mid-2026.
In SMA, genetic mutations lead to low levels of the survival motor neuron (SMN) protein. As a result, motor neurons — the nerve cells that control movement — sicken and die, leading to symptoms like muscle weakness and wasting. Several SMA treatments to boost SMN protein levels are available and can slow disease progression, but many patients experience persistent muscle weakness despite SMN-targeting therapy.
A gain in motor function can allow someone to participate in important activities of daily living, from self-care to work and social interactions, and as such, we urgently await the availability of the first-ever treatment with the potential to address the muscular component of SMA.
Scholar Rock developed apitegromab as an add-on therapy to improve muscle strength in people with SMA who are already taking SMN-targeting therapies. Apitegromab is designed to block the activity of myostatin, a protein that normally limits muscle growth.
“Muscle strength and motor function are significant unmet needs for many in the SMA community and are fundamental to independence,” Hobby said. “A gain in motor function can allow someone to participate in important activities of daily living, from self-care to work and social interactions, and as such, we urgently await the availability of the first-ever treatment with the potential to address the muscular component of SMA.”
Scholar Rock’s application seeking FDA approval of apitegromab was based mainly on data from a Phase 3 clinical trial called SAPPHIRE (NCT05156320). The trial enrolled 188 children and young adults with SMA type 2 or type 3, all of whom were taking the SMN-targeting therapies Spinraza (nusinersen) or Evrysdi (risdiplam). Participants were given apitegromab or a placebo for about a year.
The study’s main goal was to see if apitegromab would improve scores on a standardized measure of motor function called the Hammersmith Functional Motor Scale Expanded (HFMSE). Results showed it met this goal: average HFMSE scores were 1.8 points better with apitegromab than the placebo.
A measure of arm and hand function called the Revised Upper Limb Module also tended to improve more with apitegromab than the placebo, but this result was not statistically significant. No treatment-related serious side effects were reported in the SAPPHIRE study.
About the Author
