Scholar Rock Wins FDA Approval for ISEMBYLD, First Muscle-Targeted Treatment for Spinal Muscular Atrophy
Scholar Rock (NASDAQ: SRRK), a global biopharmaceutical company focused on developing therapies for rare, severe and debilitating neuromuscular diseases through its expertise in myostatin biology, announced that the U.S. Food and Drug Administration (FDA) has approved ISEMBYLD (apitegromab-mstn) for the treatment of spinal muscular atrophy (SMA) in adults and children aged 2 years and older who are receiving a survival motor neuron 2 (SMN2)-targeted treatment.
The approval represents a significant development in the treatment landscape for SMA, introducing what Scholar Rock describes as the first and only muscle-targeted therapy shown to improve motor function in individuals with SMA who are already receiving an SMN2-targeted treatment.
The approval is based on positive results from the Phase 3 SAPPHIRE study, a randomized, double-blind, placebo-controlled clinical trial that evaluated ISEMBYLD in people with SMA receiving an SMN2-targeted treatment. In the pivotal study, treatment with ISEMBYLD demonstrated a clinically meaningful improvement in motor function after one year, while participants receiving an SMN2-targeted treatment alone experienced a decline in motor function.
For the SMA community, the approval introduces a therapeutic approach designed to complement existing disease-directed treatments by directly targeting the muscle component of the disease.
First Muscle-Targeted Therapy Approved for SMA
SMA is a rare and severe neuromuscular disease characterized by irreversible loss of motor neurons and progressive muscle wasting. As motor neurons are lost, patients can experience continuing deterioration in strength and motor abilities, which can affect mobility, independence and the ability to perform everyday activities.
Although SMN2-targeted therapies have changed the treatment landscape for SMA by addressing the underlying motor neuron component of the disease, patients can continue to experience limitations in motor function.
ISEMBYLD is designed to address the muscle component of SMA through inhibition of myostatin signaling. Scholar Rock has spent years developing its expertise in myostatin biology, with the goal of developing therapies capable of improving muscle function and physical performance.
The FDA approval means ISEMBYLD can now be used in the United States in adults and children 2 years of age and older who are currently receiving an SMN2-targeted treatment.
David L. Hallal, Chairman and Chief Executive Officer of Scholar Rock, described the approval as a defining moment for the SMA community.
According to Hallal, the company is now launching what it describes as the world’s first muscle-targeted treatment for children and adults living with SMA in the United States. He also credited the company’s long-term work in myostatin inhibition, as well as clinical investigators, Cure SMA, patient advocacy organizations, patients and families who participated in the clinical development program.
Scholar Rock said its U.S. commercial organization is engaging physicians, SMA care teams and payers following the approval, while its Scholar Rock Supports program is available to provide assistance to eligible patients and caregivers.
SAPPHIRE Study Demonstrated Motor Function Improvement
The FDA approval of ISEMBYLD was supported by results from the Phase 3 SAPPHIRE study.
The pivotal trial was designed as a randomized, double-blind and placebo-controlled study, providing the key clinical evidence supporting the application.
SAPPHIRE met its primary endpoint, demonstrating a 2.2-point improvement on the Hammersmith Functional Motor Scale-Expanded (HFMSE) after one year among patients treated with ISEMBYLD at a dose of 10 mg/kg in combination with an SMN2-targeted treatment compared with patients receiving an SMN2-targeted treatment alone.
The analysis was conducted in the main efficacy population consisting of patients 2 to 12 years of age, with 103 participants included in the population. The reported nominal p-value was 0.0121.
The results also showed that a greater proportion of patients receiving ISEMBYLD achieved a meaningful increase in HFMSE scores.
Specifically, 34.2% of patients treated with ISEMBYLD experienced an increase of at least three points on the HFMSE, compared with 13.5% of patients receiving placebo. The reported odds ratio was 3.8, with a nominal p-value of 0.0125.
The findings provide clinical evidence supporting Scholar Rock’s strategy of targeting muscle function in addition to the motor neuron-directed approach of existing SMN2-targeted therapies.
HFMSE is widely used to assess motor function in individuals with SMA. Improvements in the scale can reflect meaningful changes in patients’ ability to perform various motor activities.
The results from SAPPHIRE therefore support the potential role of ISEMBYLD as an additional treatment option for individuals whose motor function remains impaired despite receiving an SMN2-targeted therapy.
Addressing an Unmet Need in SMA
The approval comes as researchers and clinicians continue to seek ways to improve functional outcomes for people living with SMA.
SMA can affect individuals differently depending on disease severity and age of onset, but progressive weakness and loss of motor function can have a substantial impact on independence and quality of life.
For many patients, maintaining the ability to move, perform self-care activities, work, interact socially and participate in daily life represents a major treatment goal.
Kenneth Hobby, President of Cure SMA, said the approval of ISEMBYLD represents a significant turning point for adults and children with SMA who have been seeking additional therapeutic options to improve motor function.
Hobby highlighted motor function as a major unmet need and emphasized its importance to maintaining independence and enabling participation in activities ranging from self-care to employment and social interactions.
The approval therefore expands the treatment approach available to eligible patients by adding a therapy specifically designed to address the muscular component of SMA.
Myostatin Biology at the Center of ISEMBYLD
ISEMBYLD is based on Scholar Rock’s work in myostatin biology.
Myostatin is a protein involved in regulating muscle growth. By targeting the myostatin pathway, researchers have sought to develop treatments capable of increasing or preserving muscle strength and function.
Scholar Rock’s development strategy for ISEMBYLD has focused on applying this biological mechanism to SMA, where muscle weakness and progressive loss of motor function remain major clinical challenges.
The company’s approach differs from therapies that primarily target the SMN pathway. Instead, ISEMBYLD is intended to directly address the muscle component of SMA.
This distinction is important because SMA is a complex neuromuscular disorder in which loss of motor neurons leads to downstream effects on muscles. Even when therapies are used to address the motor neuron component of the disease, patients may continue to have substantial muscle-related limitations.
Dr. Basil Darras, M.D., Associate Neurologist-in-Chief and Director of the Neuromuscular Center and Spinal Muscular Atrophy Program at Boston Children’s Hospital and a principal investigator in the SAPPHIRE study, said the approval marks a new era for SMA treatment.
He noted that families and neurologists consistently identify gaining motor function as a key priority and emphasized the ability to directly target muscle in people living with SMA.
Safety Profile Supported by Extensive Clinical Experience
Scholar Rock said ISEMBYLD has a well-characterized safety profile based on data from more than 500 individuals who have received apitegromab across clinical studies globally.
Some participants have received treatment for more than seven years, providing the company with longer-term experience with the therapy.
The durability of participation in the clinical development program was also reflected in the SAPPHIRE study. According to Scholar Rock, 98% of participants treated in SAPPHIRE elected to continue into the ONYX long-term extension study.
In SAPPHIRE, the most common adverse reactions reported with ISEMBYLD included upper respiratory tract infections, vomiting, cough, other viral infections, headache, gastroenteritis, pharyngitis and hypersensitivity.
Fractures were reported in 9% of patients receiving ISEMBYLD at the 10 mg/kg dose compared with 2% of patients receiving placebo.
The company has advised healthcare professionals and patients to consult the full U.S. Prescribing Information and Important Safety Information for comprehensive details regarding the approved therapy, including its risks and appropriate use.
Scholar Rock Supports Program Expands Patient Assistance
With FDA approval now secured, Scholar Rock has also initiated patient access and support services through its Scholar Rock Supports program.
The program is designed to help patients and families navigate the practical considerations associated with starting treatment with ISEMBYLD.
Support includes assistance with understanding insurance coverage, information about financial assistance programs for eligible patients, disease and treatment education, and guidance regarding site-of-care options.
The program will also assist with infusion logistics.
Depending on eligibility and other applicable considerations, ISEMBYLD infusions may be administered at different locations, including hospitals, infusion centers or patients’ homes.
Scholar Rock said it is working with leading commercial and government payers to establish reliable and broad access to ISEMBYLD for appropriate patients.
The company expects ISEMBYLD to be available for shipment in the days following the FDA approval.
This access infrastructure is particularly important for an SMA therapy intended for both pediatric and adult patients because treatment administration can require coordination among patients, caregivers, neurologists, infusion providers, insurers and other members of the healthcare team.
Rare Pediatric Disease Priority Review Voucher
In connection with the FDA approval of ISEMBYLD, Scholar Rock was awarded a Rare Pediatric Disease Priority Review Voucher.
The voucher may be used to obtain priority review for a future marketing application, providing Scholar Rock with an additional regulatory asset following the approval.
The Rare Pediatric Disease Priority Review Voucher program is designed to encourage the development of therapies for serious or life-threatening diseases affecting pediatric populations.
For Scholar Rock, the voucher adds strategic value to the ISEMBYLD approval and could potentially be applied to a future marketing application that meets the applicable regulatory requirements.
Commercial Launch Begins in the United States
The FDA decision marks the transition of ISEMBYLD from clinical development into commercial availability in the United States.
Scholar Rock is now preparing to support healthcare providers and SMA care teams as they evaluate the treatment for eligible patients.
The company’s commercial organization is working with physicians and payers, while Scholar Rock Supports is providing resources intended to help patients and caregivers navigate access.
The launch also represents the culmination of years of research into myostatin inhibition.
Scholar Rock said previous industry efforts to develop myostatin inhibitors had not successfully translated into an approved therapy, making the ISEMBYLD approval a significant milestone for the company’s scientific platform.
The therapy’s approval for patients already receiving SMN2-targeted treatment also establishes its role within the broader SMA treatment landscape rather than positioning it as a replacement for existing SMN2-directed therapies.
Next Steps for ISEMBYLD
With FDA approval secured, Scholar Rock’s focus will shift toward expanding patient access and supporting the integration of ISEMBYLD into routine SMA care.
The company will continue working with healthcare providers, treatment centers, payers and patient organizations to facilitate access for eligible adults and children.
For patients and families, the availability of a muscle-targeted treatment represents an additional option in the ongoing effort to preserve and improve motor function.
The SAPPHIRE results provide the clinical foundation for the approval, demonstrating that patients receiving ISEMBYLD alongside an SMN2-targeted treatment experienced a statistically supported and clinically meaningful improvement in HFMSE scores compared with those receiving an SMN2-targeted treatment alone.
At the same time, the long-term clinical experience accumulated across the apitegromab program provides additional information about the treatment’s safety profile.
Scholar Rock plans to continue communicating with the SMA community as ISEMBYLD becomes available in the United States. The company’s patient support infrastructure is already being activated, with treatment expected to begin shipping shortly after approval.
The company will also host a conference call and webcast on September 14, 2026, at 8:00 a.m. Eastern Time to discuss the FDA approval and the ISEMBYLD program. The live webcast will be available through the Events and Presentations section of Scholar Rock’s investor website, with a replay expected to remain available for approximately 90 days.
Overall, the FDA approval of ISEMBYLD represents a major development in SMA treatment, introducing a therapy designed to directly target muscle function for patients already receiving SMN2-targeted treatment. For Scholar Rock, the decision validates its long-term focus on myostatin biology and establishes ISEMBYLD as a new commercial product in the U.S. rare-disease market.
For the SMA community, the approval provides an additional therapeutic approach aimed at improving motor function, an outcome that patients, families and clinicians have identified as a critical unmet need. As commercial availability begins, Scholar Rock will focus on ensuring eligible patients can access the therapy while continuing to support the healthcare professionals responsible for delivering treatment.
About ISEMBYLD
ISEMBYLD is a fully human monoclonal IgG4 antibody that binds to promyostatin and latent myostatin and inhibits the activation of myostatin, blocking myostatin signaling. ISEMBYLD is approved in the United States for the treatment of spinal muscular atrophy (SMA) in adults and pediatric patients 2 years of age and older who are currently receiving a survival motor neuron 2 (SMN2)-targeted treatment.