US, EU regulators to review higher-dose Spinraza for use in SMA
Biogen seeking approval of new regimen based on positive clinical trial data
Regulators in the U.S. and the European Union have agreed to review Biogen’s applications seeking approval of a higher dose of Spinraza (nusinersen) for all types of spinal muscular atrophy (SMA) in individuals of all ages — a regimen the therapy’s developer says may provide more effective treatment for patients.
According to Biogen, the U.S. Food and Drug Administration accepted its supplemental new drug application for the new dosing regimen. Meanwhile, the European Medicines Agency, which decides on approvals for the EU, validated the company’s application for higher dose Spinraza.
This still-experimental dosing regimen involves faster loading with two doses of 50 mg given 14 days, or two weeks, apart, and a maintenance dose of 28 mg every four months thereafter. That maintenance dose is higher than the currently approved dose of 12 mg every four months.
“We are pleased to announce that our applications for the higher dose regimen of nusinersen are now under review in the U.S. and Europe. … We expect that this higher dose regimen will offer meaningful benefits to patients and their families,” Stephanie Fradette, head of Biogen’s neuromuscular development unit, said in a company press release.
“This milestone reflects our steadfast commitment to advance treatment options for individuals with SMA,” Fradette added. “We are deeply thankful for the unwavering support of the trial participants, their families, site staff, and the SMA community without whom these advancements would not have been possible.”
DEVOTE trial tested higher Spinraza doses in 145 SMA patients
For Thomas Crawford, MD, who codirects the Muscular Dystrophy Association Clinic at Johns Hopkins Medicine in Baltimore, this Biogen update is “a significant step forward for the community.”
“Continued progress to improve upon the remarkable initial successes in SMA [treatment] necessitates an innovative approach,” Crawford said.
Spinraza, the first disease-modifying therapy approved for SMA, is given via intrathecal injection, meaning directly into the spinal canal. The first dose is usually given as soon as possible after patients receive their diagnosis, and is followed by three more doses at the two-, four-, and nine-week time points. Doses then are given every four months for as long as the treatment offers benefits to the patient.
The applications for approval of a new regimen for Spinraza are based on positive data from DEVOTE (NCT04089566), a company-sponsored Phase 3 clinical trial that wrapped up in 2024. That trial tested how safe a higher Spinraza dose is and how well it works in 145 patients across all ages and main types of SMA.
Results from the DEVOTE study have shown us that the higher dose regimen of [Spinraza] can enable meaningful clinical benefits while maintaining a safety profile broadly consistent with the approved 12 mg regimen.
The DEVOTE trial was divided into three parts. Part A tested the safety and tolerability of Spinraza in six patients, ages 6 to 13, when given at the higher-dose regimen, which included two maintenance doses of 28 mg. The higher dose was well tolerated, with four patients experiencing mostly mild side effects.
Part B compared the higher-dose regimen against the currently approved dose in 75 patients with infantile-onset SMA who had never received treatment for the condition. As untreated controls, it included patients from ENDEAR (NCT02193074), the Phase 3 clinical trial that provided the basis for approval of the 12 mg dose.
After six months, the higher dose resulted in significant improvements in motor function, measured with the Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND), compared with the untreated controls, whose motor function worsened over time.
The higher dose was linked to a lower risk of death or need for permanent ventilation to help with breathing for participants as compared with the group of untreated patients. It also was tied to a lower risk of hospitalization and serious respiratory events for the treated patients relative to those untreated. The higher dose also tended to be better than the 12 mg dose on these measures.
The open-label Part C tested how safe the transition to the higher-dose regimen was in 40 children and adults who had been receiving Spinraza at the approved dosing regimen for at least one year. Patients received a single dose of 50 mg four months after their last intrathecal injection of 12 mg, followed by two doses of 28 mg spaced by four months. Data suggested improvements in motor function after the transition.
According to Crawford, “results from the DEVOTE study have shown us that the higher dose regimen of [Spinraza] can enable meaningful clinical benefits while maintaining a safety profile broadly consistent with the approved 12 mg regimen.”
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