FDA OKs Isembyld as first muscle-strengthening therapy for SMA
More than a year after the U.S. Food and Drug Administration (FDA) rejected the muscle-strengthening agent apitegromab for spinal muscular atrophy (SMA) due to manufacturing issues, the agency has approved the add-on treatment for use by certain people with the rare genetic condition.
The therapy’s developer Scholar Rock will be marketing the medication under the brand name Isembyld. According to its website, “Isembyld is the first and only FDA-approved treatment to directly target the muscle in SMA.”
The infusion treatment is specifically indicated for individuals with SMA, ages 2 and older, who are taking medications targeting the SMN2 gene, which makes a small amount of a vital protein lacking in people with SMA. Two such medications are Spinraza (nusinersen) and Evrysdi (risdiplam), both widely approved.
“[The] FDA approval of Isembyld marks a defining moment for the SMA community as we now launch the world’s first-ever muscle targeted treatment for children and adults living with SMA in the U.S.,” David L. Hallal, chairman and CEO of Scholar Rock, said in a company press release announcing the FDA decision, which came Friday.
Scholar Rock, which had already been gearing up for a commercial launch, said the medication will be available to ship in the next few days. The company offers a program called Scholar Rock Supports that provides assistance to patients, with educational resources and information on insurance coverage and financial aid for qualifying individuals.
“Our U.S. commercial team is now engaging physicians, SMA care teams, and payers on behalf of the SMA community and our Scholar Rock Supports team stands ready to provide dedicated, comprehensive assistance to patients and caregivers,” Hallal said.
SMA is caused by mutations in the gene SMN1, which provides instructions to make a protein called SMN that’s necessary for the survival of motor neurons, the nerve cells that control movement. Lacking SMN, motor neurons sicken and die, leading to SMA symptoms such as muscle weakness and wasting.
To date, four disease-modifying treatments have been FDA-approved for SMA, all of which slow disease progression by boosting SMN protein levels to preserve motor neuron health. Spinraza and Evrysdi both work by modulating the activity of SMN2, a gene that functions like a backup for SMN1. Meanwhile, the gene therapies Itvisma (onasemnogene abeparvovec-brve) and Zolgensma (onasemnogene abeparvovec-xioi) treat SMA by delivering a healthy copy of the SMN1 gene to motor neurons.
Muscle weakness common in SMA despite treatment
Although disease-modifying treatments can slow SMA progression, many patients nonetheless experience notable muscle weakness. Isembyld is an antibody-based therapy designed to block myostatin, a protein that normally prevents unneeded muscle growth. By blocking this protein, the therapy essentially aims to take the brakes off muscle growth so as to improve strength and mobility for patients.
“This approval represents an important evolution in how we think about treating spinal muscular atrophy,” Angela Lek, PhD, chief research officer at the Muscular Dystrophy Association, told SMA News Today. “We are beginning to see the potential of complementary approaches that address different aspects of the disease, including therapies that target the underlying biology of SMA alongside treatments designed to preserve or improve muscle function. That is a meaningful shift for people living with SMA and their families.”
According to Lek, new treatments such as Isembyld have the potential to create much-needed positive change for those with the progressive disease.
“As these approaches continue to advance, our expectations can also evolve,” Lek said. “The continued development of therapies that can work together gives us even more reason to be optimistic about what the future of SMA treatment may hold.”
The approval of Isembyld as the first-ever treatment to directly target the muscular component of SMA is a significant turning point for adults and children who have been waiting for innovative therapeutic options to improve motor function.
According to Isembyld’s prescribing information, common side effects of the newly-approved therapy include headache, vomiting, cough, stomach flu, sore throat, and other viral infections. Allergic reactions and respiratory tract infections also are common.
The prescribing information also notes that Isembyld may increase the risk of broken bones. Animal data suggest the therapy may impair fertility, and that it may also cause problems with a developing fetus if used during pregnancy.
Isembyld is given intravenously, or by infusion into the bloodstream, every four weeks. Infusions may be given at hospitals, infusion centers, or at home, according to Scholar Rock. The company is also developing an injection version of the therapy, to be given subcutaneously, or under the skin, to maximize convenience for patients.
“The approval of Isembyld as the first-ever treatment to directly target the muscular component of SMA is a significant turning point for adults and children who have been waiting for innovative therapeutic options to improve motor function,” said Kenneth Hobby, president of Cure SMA, a U.S.-based advocacy group.
“We appreciate the FDA’s recognition, as reflected in this approval that supports access for a broad population within the SMA community, that improving motor function is a significant unmet need that must be addressed with urgency,” Hobby said. “Such improvements are fundamental to maintaining independence and to enabling participation in important activities of daily living from self-care to work and social interactions.”
A rocky road to approval for Isembyld
Scholar Rock’s application seeking FDA approval of Isembyld was based on data from the Phase 3 SAPPHIRE clinical trial (NCT05156320), completed in 2024.
SAPPHIRE tested the add-on Isembyld against a placebo in nearly 200 young people with SMA who were taking Spinraza or Evrysdi. The trial met its main goal, demonstrating that Isembyld outperformed the placebo in improving motor function, assessed with a standard measure. The most dramatic effects were seen in patients who were younger and started treatment earlier.
Basil Darras, MD, a principal investigator in the SAPPHIRE study at Boston Children’s Hospital, said the FDA’s approval of Isembyld “marks a new era for the treatment of SMA.”
“As neurologists, families consistently tell us that their top priority is gaining motor function, and we are now able to directly target the muscle, not just the motor neuron, for people living with SMA,” Darras said.
Despite the positive trial data, Isembyld’s road toward FDA approval was rocky.
Scholar Rock initially submitted an application seeking FDA approval in early 2025 — but later that year, the regulator agency rejected the application. At the time, the FDA didn’t raise any concerns related to the clinical data for Isembyld, but issues were found at a third-party fill-finish facility. This type of facility is responsible for the final stages of packaging a medication, such as ensuring that the product is sterile.
After working with the fill-finish facility to address the FDA’s concerns, Scholar Rock resubmitted its application. But the FDA once again found issues at the same facility, called Catalent Indiana (now fully owned and operated by Novo Nordisk), at an inspection earlier this year. To keep the application on track, Scholar Rock dropped that facility and brought in a second fill-finish facility.
Issues at the fill-finish facility have also complicated Scholar Rock’s efforts to seek Isembyld approval in the European Union. The company had originally applied for EU approval with Catalent Indiana as its only listed fill-finish facility, but following the second failed FDA inspection, Scholar Rock has been working to also switch the facility listed on that application.
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