High-dose Spinraza regimen approved in Europe for spinal muscular atrophy
Decision adds new dosing option for children and adults with SMA
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- The European Commission approved a high-dose Spinraza regimen for people with 5q spinal muscular atrophy (SMA).
- The updated regimen includes higher loading doses followed by higher maintenance dosing.
- Clinical trial data showed improved motor function and lower risk of death compared with untreated patients in earlier studies.
The European Commission has approved a new high-dose regimen of Spinraza (nusinersen) for people with 5q spinal muscular atrophy (SMA).
“We are proud to introduce the high dose regimen of SPINRAZA, which we have developed to address the evolving needs of individuals living with SMA, and are deeply committed to bringing it to the European SMA community as quickly as possible,” Priya Singhal, MD, executive vice president and head of development at Spinraza’s maker Biogen, said in a company press release. “We are grateful for all of the contributions of the SMA community who made today’s approval possible.”
5q SMA accounts for the vast majority of SMA cases and is caused by mutations in the SMN1 gene. These mutations result in low levels of a protein called SMN, which is essential for the health of motor nerve cells. Without enough SMN protein, these nerve cells gradually degenerate.
How Spinraza works to raise SMN protein levels
Spinraza works by increasing levels of SMN protein levels through its effects on a related gene called SMN2, which serves as a partial backup for the faulty SMN1 gene in people with SMA. By boosting SMN protein levels, the therapy aims to support the health of motor nerve cells and slow disease progression. Spinraza is given by injection into the spinal canal and was the first treatment for SMA to receive widespread regulatory approval. The European Commission first authorized its use in 2017.
“Since its approval in the European Union in 2017, SPINRAZA has helped set a new standard in patient care and treated more than 10,000 infants, children, teens and adults worldwide,” Singhal said.
Under its original approval, Spinraza is given at a dose of 12 mg, with the first three doses administered every other week, followed by a fourth dose one month later. Maintenance doses are then given every four months.
The new approval allows for a higher-dose regimen in which patients receive two 50 mg loading doses given two weeks apart, followed by a 28 mg maintenance dose every four months. Patients already receiving the previously approved regimen may transition by replacing their next scheduled 12 mg dose with a single 50 mg dose, followed by 28 mg maintenance doses every four months.
Nicole Gusset, CEO of SMA Europe, said approval of the new high-dose regimen “highlights the importance of sustained research and investment, contributing to a wider range of possibilities that may enable more tailored approaches to SMA care over time.”
“As a community, we welcome advances that expand options for people living with SMA and reinforce continued innovation in SMA care,” Gusset added.
Approval backed by clinical trial data
The European Commission’s approval of the higher-dose regimen was supported in part by data from the Phase 3 DEVOTE trial (NCT04089566). In that study, previously untreated children with SMA who received the higher-dose regimen showed improvements in motor function and a lower risk of death compared with untreated children from an earlier Spinraza study. The DEVOTE trial also found that patients who switched from the original dosing regimen to the higher-dose regimen tended to show motor function improvements. Safety findings for the higher-dose regimen were consistent with the established safety profile of the original 12 mg dose.
“The DEVOTE results provide encouraging evidence that this new dosing option could deliver meaningful treatment outcomes with a safety profile generally consistent with the 12 mg dosing regimen,” said Eugenio Mercuri, MD, PhD, a professor at the Catholic University in Rome, Italy. “I have witnessed the remarkable strides that have been made in treating SMA, but it is clear [that] challenges remain. The European Commission approval of the high dose regimen of SPINRAZA is an important step toward addressing those challenges and advancing how we care for people living with SMA.”
The high-dose Spinraza regimen is already approved in Japan and is currently under regulatory review in the U.S., with a decision expected in April.
