Biogen Publishes DEVOTE Study Showing Benefits Of High-Dose Nusinersen In Spinal Muscular Atrophy, Highlights Faster-Loading, Higher-Dose SPINRAZA Regimen

Biogen announced that Nature Medicine has published results from the Phase 2/3 DEVOTE study assessing a higher-dose regimen of nusinersen for people living with spinal muscular atrophy (SMA). The regimen includes two rapid 50 mg loading doses given two weeks apart, followed by 28 mg maintenance doses every four months, higher and faster than the currently approved 12 mg SPINRAZA schedule. The findings showed that the intensified dosing approach was both safe and effective across patients of different ages, treatment histories, and functional levels.

In the pivotal portion of the study, treatment-naïve symptomatic infants who received the high-dose regimen achieved statistically significant gains in motor function measured by the CHOP-INTEND scale when compared with a matched untreated group from Biogen’s earlier ENDEAR trial. The improvement was substantial and consistent across secondary endpoints, and several biomarkers and efficacy measures also trended in favor of the higher dose versus the standard regimen.

“One of the most notable changes seen with the higher dose regimen was a more rapid reduction in neurofilament, a marker of neurodegeneration. In DEVOTE, treatment with the high-dose regimen led to improvement across important domains like motor and bulbar function, respiratory health and hospitalizations, and survival,” said Richard Finkel, M.D., director, Center for Experimental Neurotherapeutics (CENT) at St. Jude Children’s Research Hospital. “Publication of the DEVOTE results in Nature Medicine further validate the importance of these data and the future role that I expect the high dose regimen will play as we look to continue to improve outcomes for people living with SMA.”

Another part of the study followed children and adults who switched to the higher dose after several years on the 12 mg regimen. These participants demonstrated modest but meaningful functional improvements over time, with increases seen on commonly used motor-assessment scales after transitioning to the intensified dosing schedule.

“The publication of the DEVOTE data are an important step in our commitment to bring the high dose regimen of nusinersen to people living with SMA as quickly as possible,” said Stephanie Fradette, Pharm.D., Head of the Neuromuscular Development Unit at Biogen. “We are grateful to the participants, their families, study investigators and site staff, and our co-authors who have made the DEVOTE study and publication of these results a reality.”

Safety findings were broadly consistent with what has previously been observed with nusinersen. The most frequent adverse events were respiratory-related infections and fever, while serious events were mainly pneumonia and respiratory complications. The high-dose version of SPINRAZA is already approved in the European Union and Japan, and a U.S. regulatory decision is expected by early April.