Positive topline results from study of higher dose regimen of nusinersen, showing significant benefit in treatment of spinal muscular atrophy

The investigational higher dose regimen of nusinersen comprises a more rapid loading regimen, two 50 mg doses 14 days apart, and a higher maintenance regimen, 28 mg, every 4 months, compared to the approved nusinersen regimen (Spinraza).

The study met its primary endpoint at six months, achieving a statistically significant improvement in motor function in infants who received the higher dose regimen as compared to a prespecified matched sham (untreated) control group from the ENDEAR study.

“While there has been remarkable progress in the treatment of SMA, there remains significant unmet need. Building on the well-characterized profile of Spinraza established over the past 10 years, we continue to explore the potential for maximizing efficacy outcomes while maintaining our commitment to safety,” said Stephanie Fradette, Pharm.D., Head of the Neuromuscular Development Unit at Biogen. “The encouraging topline results from DEVOTE show that the higher dose regimen can slow neurodegeneration faster, as shown by greater reductions in neurofilament at day 64 relative to the approved dose. Over time, the higher dose regimen led to meaningful clinical benefit in infants with symptomatic SMA. We look forward to sharing the detailed results with the SMA community and health authorities.”

DEVOTE is a three-part study that enrolled 145 patients across ages and SMA types. The pivotal Part B cohort was comprised of treatment-naïve children with infantile-onset SMA (n=75) who were randomized 2:1 to receive the investigational higher dose regimen of nusinersen or the approved 12 mg regimen (comprising four loading doses and maintenance doses every four months).

The primary endpoint of Part B measured the change from baseline on the Children's Hospital of Philadelphia-Infant Test of Neuromuscular Disorders (CHOP-INTEND) at six months comparing the higher dose regimen of nusinersen to a matched, untreated sham control group from the Phase III ENDEAR study. ENDEAR is one of the two pivotal studies that formed the basis of regulatory approval for Spinraza 12 mg.

The higher dose cohort showed statistically significant improvement over the matched sham comparator on the primary endpoint of change in CHOP-INTEND from baseline to six months (least squares mean difference: 26.19; p<0.0001). results favored the higher dose regimen relative to sham across secondary endpoints and trended in favor of the higher dose regimen over the currently approved 12mg regimen on key biomarker and efficacy measures. the higher dose regimen was generally well tolerated, with reported adverse events generally consistent with sma and the known safety profile of nusinersen. the percentage of serious adverse events was lower in the higher dose regimen (60%; 30) as compared to the 12 mg group (72%; 18). detailed results from devote will be presented at upcoming medical conferences.

More information about the DEVOTE study (NCT04089566) is available at clinicaltrials.gov. Nusinersen is currently commercialized under the brand name Spinraza and the FDA-approved dose is 12 mg.