New high-dose Spinraza moves forward after positive EU opinion
CHMP backs higher nusinersen dose based on data from Phase 3 trial
- The EU committee recommended a high-dose Spinraza regimen for SMA treatment.
- Phase 3 DEVOTE trial data showed improved motor function and survival for SMA patients.
- This high-dose Spinraza is approved in Japan and under review in the U.S.
A high-dose regimen of nusinersen — the active ingredient in Spinraza — has been recommended for approval to treat spinal muscular atrophy (SMA) by the Committee for Medicinal Products for Human Use (CHMP), a branch of the European Medicines Agency.
The decision was based on positive data from the Phase 3 DEVOTE trial (NCT04089566), which tested the high-dose regimen in people who had never received nusinersen or who were switching from the standard approved dosing regimen.
The experimental regimen uses faster loading with two 50 mg doses, given 14 days apart, followed by a 28 mg maintenance dose every four months. A final decision from the European Commission is expected in January 2026.
High-dose nusinersen already approved in Japan, under review in U.S.
The high-dose regimen has already been approved in Japan and is now under review with the U.S. Food and Drug Administration (FDA), with a decision expected by April 3, 2026. Earlier this year, the FDA declined to approve this regimen and requested updates to technical information be included in the application.
“The CHMP’s positive opinion for the high dose regimen of nusinersen represents a promising advancement in our commitment to support the evolving needs of individuals living with SMA and deliver therapies that can enhance patient outcomes,” Priya Singhal, MD, executive vice president and head of development at Biogen, said in a company press release.
SMA is usually caused by mutations in the SMN1 gene that result in low levels of SMN protein and the progressive loss of motor neurons — the nerve cells that control movement.
Spinraza is a widely approved SMA treatment to help slow or halt disease progression. It works by increasing the levels of the SMN protein produced from SMN2, a backup gene for SMN1. The therapy is administered by injection into the spinal canal, with four loading doses of 12 mg — the first three every 14 days and the fourth 30 days later — followed by a 12 mg maintenance dose every four months.
Phase 3 DEVOTE trial assessed safety and efficacy of higher Spinraza dose
The DEVOTE trial tested the safety and efficacy of the higher Spinraza dose in 145 people with SMA. The main part of the trial enrolled 75 children with infantile-onset SMA, not previously treated, who were randomly assigned to receive either the higher dose or the approved dosing regimen.
Results showed those who received the high-dose regimen had significant improvements in motor function compared with historical untreated controls from the ENDEAR Phase 3 trial (NCT02193074). The higher dose was also associated with a 68% lower risk of death or permanent ventilation compared with those untreated controls.
The DEVOTE trial also included 40 additional children and adults with SMA who switched from the approved regimen to the high-dose formulation. In these patients, motor function tended to improve after the switch.
The high-dose regimen was generally well tolerated, with adverse events in line with Spinraza’s known safety profile. The most common adverse events in part B of the trial included pneumonia, COVID-19, and malnutrition.
“The positive CHMP opinion for the high dose regimen of nusinersen is an important milestone for the SMA community,” said Eugenio Mercuri, MD, PhD, professor at the Catholic University in Rome, Italy. “Based on the results from the DEVOTE study and my experience with patients receiving this novel regimen, I am confident that high dose nusinersen has the potential to bring meaningful benefits to people living with SMA.”
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