Higher Dose Nusinersen Shows Promising Results in SMA at World Muscle Society Congress

Biogen Inc. recently announced detailed findings from Parts B and C of the Phase 2/3 DEVOTE study. This study evaluates the safety and efficacy of a higher dose regimen of nusinersen for treating spinal muscular atrophy (SMA). The higher dose involves a rapid loading phase with two 50 mg doses administered 14 days apart, followed by a maintenance dose of 28 mg every 4 months. This investigational regimen is compared to the currently approved 12 mg dose of nusinersen, marketed as SPINRAZA®.

The detailed results, presented at the World Muscle Society (WMS) 2024 Congress, emphasize the potential benefits of the higher dose regimen in addressing unmet medical needs in SMA. The study enrolled 145 participants across various age groups and SMA types.

Part B of the DEVOTE study included a pivotal cohort of symptomatic, treatment-naïve infants (n=75). These infants received the higher dose regimen and showed significant improvements in motor function, as measured by the Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND), outperforming a matched sham control group from the Phase 3 ENDEAR study. The higher dose group demonstrated a 94% reduction in plasma neurofilament light chain (NfL) levels, a marker of neurodegeneration, by Day 183, compared to a 30% reduction in the sham group. This indicates a more rapid slowing of neurodegeneration with the higher dose regimen.

Additionally, the higher dose regimen resulted in improved outcomes in motor function assessments, such as the Hammersmith Infant Neurological Exam section 2 (HINE-2) and overall survival rates. It reduced the risk of death or permanent ventilation by nearly 68% compared to the sham group and by about 30% compared to the 12 mg regimen, although the latter was not statistically significant.

In the later-onset cohort of Part B, participants receiving the higher dose regimen showed greater improvements in motor function assessments like the Hammersmith Functional Motor Scale – Expanded (HFMSE) and the Revised Upper Limb Module (RULM) at Day 302, compared to those receiving the 12 mg dose and matched control groups.

Part C of the DEVOTE study involved participants aged 4-65 who transitioned from the approved 12 mg dose to the higher dose regimen. These participants experienced improvements in motor function, with mean increases in HFMSE and RULM scores at Day 302.

The higher dose regimen was generally well tolerated, with a safety profile similar to the approved 12 mg regimen. Common adverse events included respiratory infections, fever, constipation, headache, vomiting, and back pain. The frequency of adverse events leading to study withdrawal and death was highest in the treatment-naïve cohort of Part B.

Kenneth Hobby, President of Cure SMA, highlighted that while significant progress has been made in SMA treatment over the past decade, there are still gaps to address. The findings from the DEVOTE study offer promising potential for further improving motor function and daily living activities for people with SMA.

Biogen plans to submit global regulatory applications for the approval of the 50/28 mg higher dose nusinersen regimen. Currently, nusinersen (SPINRAZA®) is approved in over 71 countries at the 12 mg dose and has been administered to more than 14,000 individuals worldwide. The higher dose regimen aims to enhance the efficacy and address the remaining unmet needs in the SMA patient community.