Scholar Rock works to bring SMA treatment to patients worldwide
‘Our work does not stop’ with US approval, says president of R&D
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- Scholar Rock is working to bring its new SMA treatment, Isembyld, to patients worldwide.
- The FDA recently approved the drug as the first muscle-strengthening treatment for SMA.
- The Muscular Dystrophy Association's chief research officer says the treatment gives patients a new tool, as it targets the muscle itself.
Scholar Rock is working to bring spinal muscular atrophy (SMA) treatment Isembyld (apitegromab-mstn) to patients worldwide, following U.S. Food and Drug Administration (FDA) approval of the infusion therapy as the first muscle-strengthening agent to treat the disease.
“Our work does not stop with the US approval,” Akshay Vaishnaw, MD, PhD, president of research and development at Scholar Rock, said in an interview with SMA News Today. “Our ambition is that globally, any patient with SMA who can benefit from ISEMBYLD will have access to it.”
Following issues at a manufacturing plant that delayed U.S. approval, Scholar Rock recently resubmitted an application seeking approval of Isembyld in the European Union. The company is on track to submit a similar application seeking approval in Japan before the end of the year.
“These efforts reflect our long-term commitment to continue listening to the SMA community and pursuing new possibilities for people living with rare neuromuscular diseases,” Vaishnaw said.
SMA is caused mainly by mutations that lead to SMN protein deficiency. Without working SMN protein, motor neurons (the nerve cells that control movement) sicken and die, leading to muscle weakness that worsens as time goes on.
Recent years have brought ‘extraordinary’ progress on treatments
For almost all of human history, nothing could be done to stop the loss of motor neurons in SMA. That changed a decade ago with the approval of the first disease-modifying therapy for SMA. Disease-modifying therapies can increase SMN protein levels, preserving motor neuron health.
“The progress in [SMA] treatment over the past decade has been extraordinary,” said Angela Lek, PhD, chief research officer at the Muscular Dystrophy Association. “Disease-modifying therapies have changed what is possible for many people living with SMA by addressing the underlying cause of the disease and helping preserve motor neurons.”
Although disease-modifying treatments can help prevent SMA from worsening, they can’t repair damage that’s already occurred. Consequently, many people with SMA still experience notable muscle weakness even with disease-modifying treatment.
“Even when someone is receiving one of these treatments, muscle weakness can continue to affect movement, strength and day-to-day activities,” Lek told SMA News Today.
Angela Lek, PhD, is chief research officer at the Muscular Dystrophy Association. (Photo courtesy of MDA)
Isembyld works by blocking the activity of myostatin, a protein that normally prevents excess muscle growth. In doing so, the therapy aims to improve muscle strength. Scholar Rock developed Isembyld for use as an add-on therapy in SMA patients receiving disease-modifying treatment.
“One simple way to think about it is that these treatments are addressing different parts of the problem,” Lek said. “SMN-targeted therapies help address the underlying cause of SMA by increasing levels of SMN protein, which is important for motor neurons. Isembyld works directly in muscle by blocking myostatin, a protein that normally acts as a kind of natural brake on muscle growth and development.”
Lek noted that the goal of Isembyld “isn’t simply to make muscles bigger. It is to help improve the muscle’s ability to contribute to movement and strength.”
The recent FDA approval covers Isembyld’s use in patients ages 2 and older who are receiving disease-modifying treatments such as Spinraza (nusinersen) or Evrysdi (risdiplam) that target the SMN2 gene. The approval was based on data from a Phase 3 trial called SAPPHIRE (NCT05156320), which tested the therapy against a placebo in SMA patients taking Spinraza or Evrysdi.
“We have consistently heard from patients and families that progressive muscle weakness remains a significant challenge, even with available treatments,” Vaishnaw said. “The approval of the first SMA treatment to directly target muscle reflects an important evolution in how we can think about addressing that need – with the goal not only of preserving motor function but helping people achieve meaningful gains.”
Credit goes to the community
Vaishnaw said the treatment’s approval was only possible because of years of advocacy from the SMA community. “We believe the FDA approval of ISEMBYLD reflects not only scientific achievement, but also the strength of a community that has never stopped advocating,” he said.
The SAPPHIRE study demonstrated that add-on Isembyld outperformed a placebo at improving a standard measure of motor function. Vaishnaw and Lek both noted that, since each person with SMA’s motor function prior to treatment is unique, specific experiences with Isembyld can look very different from person to person.
“For one person, an improvement could mean being able to perform a movement more easily or with less assistance,” said Lek. “For another, it could mean greater ability to reposition themselves, maintain a position, move an arm or perform another task that is important to them. The significance really depends on which abilities are most relevant to that person.”
To better understand patients’ experiences, Vaishnaw and other researchers at Scholar Rock interviewed patients and caregivers who participated in SAPPHIRE and other trials of Isembyld. Patients said the muscle-strengthening agent “has helped them gain new skills, such as being able to sit on their own, being able to crawl, or brush teeth,” Vaishnaw said.
“They told us they’ve noticed that their hands are stronger, they can use markers, open a container, or sit or stand on their own,” he added. “Not all individuals living with SMA will experience all these benefits, and it should be kept in mind that even a discrete increase in one aspect of motor function, [such as] ability to sit, can matter greatly.”
Data from SAPPHIRE showed that motor function improvements were generally most dramatic among patients who were younger and started treatment earlier. “But I would not want people who have been living with SMA for many years to look at these results and assume that this therapy isn’t relevant to them,” Lek said. “Adults and people with more established disease have different needs and goals, and maintaining or improving function can be meaningful at every stage of life.”
“The right approach will depend on the person’s age, disease history, current abilities, other treatments and personal goals, in discussion with their healthcare team,” she said.
Common side effects of Isembyld include infections, stomach flu, vomiting, cough, headache, and allergic reactions. The therapy’s prescribing information also carries warnings related to the risk of broken bones. Lek and Vaishnaw both said that SMA patients interested in Isembyld should talk with their healthcare providers about the potential benefits and risks of the therapy.
“For someone considering treatment, I would encourage them to ask their care team what these risks mean in the context of their own health and circumstances,” said Lek. “In particular, it may be important to discuss bone health, fracture history and any other factors that could affect their individual risk.”
Vaishnaw said, “Fractures can be a particular concern for people living with SMA, as they are a known complication of the disease, but importantly, the fracture rates observed in our clinical studies were well within rates reported in studies for the SMA population. Additionally, no fracture was considered related to treatment by clinical investigators, no patient discontinued treatment or withdrew from the study because of a fracture, and patients who experienced fractures were able to remain on treatment as their fractures resolved.”
“Just as importantly, people should think about what they hope treatment might help them achieve,” Lek said. “Is there a particular activity they want to make easier? Is maintaining a certain level of independence important?”
“Having that conversation with your care team can help you understand whether this treatment fits your personal goals,” Lek added. “There is no single treatment decision that is right for every person with SMA. The important thing is having the information and support needed to make an informed decision with your healthcare team.”
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