Scholar Rock asks FDA to approve apitegromab for SMA
Planned OPAL clinical trial to test add-on therapy in patients younger than 2
Scholar Rock is asking the U.S. Food and Drug Administration (FDA) to approve apitegromab, its experimental add-on therapy designed to boost motor function in people with spinal muscular atrophy (SMA).
“With the strength of our Phase 3 data as the foundation of our submission, we look forward to continuing to work closely with the FDA through the review of our BLA [biologics license application] on behalf of patients and families living with SMA,” Jing Marantz, MD, PhD, chief medical officer of Scholar Rock, said in a company press release.
Scholar Rock is requesting priority review for its application which, if granted, would shorten the review time to six months instead of the usual 10 months. The company noted it is preparing a similar application seeking approval of apitegromab in Europe, which it expects to submit in the next month or two.
SMA is mostly caused by mutations in the SMN1 gene, resulting in abnormally low levels of the SMN protein. Without this protein, motor neurons, or the nerve cells that control voluntary movement, sicken and die, ultimately leading to SMA symptoms such as muscle weakness.
Several therapies are approved for SMA that work by boosting SMN protein levels. Apitegromab is designed to be used in combination with SMN-targeting therapies.
Apitegromab designed to block activity of myostatin protein
Rather than address the root cause of the disease, apitegromab is designed to block the activity of myostatin, a protein that normally helps to limit muscle growth. By blocking myostatin, the therapy works to increase muscle growth, thereby improving patients’ motor function. In clinical trials, the therapy has been administered by infusions into the bloodstream every four weeks.
Scholar Rock’s FDA application is based primarily on data from a Phase 3 clinical trial called SAPPHIRE (NCT05156320), which tested apitegromab against a placebo in young adults and children with SMA type 2 or 3 who could sit independently and were taking the SMN-targeting therapies Spinraza (nusinersen) or Evrysdi (risdiplam).
Results from SAPPHIRE showed that, after a year of treatment, average scores on the Hammersmith Functional Motor Scale Expanded (HFMSE), a standard motor function measurement, were 1.8 points better with apitegromab than with the placebo. Apitegromab was given at 10 or 20 mg/kg. The difference in HFMSE improvement between the two doses was not considered statistically significant.
“We are gratified that in patients already on a SMN-targeted treatment, the SAPPHIRE trial met its primary endpoint for the main efficacy population showing a statistically significant 1.8-point improvement for patients receiving apitegromab compared to placebo, as measured by the Hammersmith Functional Motor Scale-Expanded at week 52,” Marantz said.
Scholar Rock’s application for apitegromab also includes data from the earlier Phase 2 TOPAZ clinical trial (NCT03921528), which likewise suggested the therapy led to improved motor function for SMA patients taking SMN-targeting therapies.
The SAPPHIRE and TOPAZ studies enrolled SMA patients ages 2 to 21. Scholar Rock said it is planning to launch another clinical trial mid-2025, dubbed OPAL, that will test the therapy in patients younger than 2. Like the other trials, OPAL is expected to test apitegromab as an add-on in patients who have been or are continuing to be treated with SMN-targeting therapies.
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