- Findings from Part B and Part C of the DEVOTE study support the clinical benefits of a higher dose regimen of nusinersen (50/28 mg) in both individuals previously treated and treatment-naïve to nusinersen
- Investigational regimen also shows more rapid slowing of neurodegeneration, as measured by neurofilament
- Biogen plans to submit regulatory applications around the world for approval of the nusinersen higher dose regimen
Biogen today announced detailed results from Part B and Part C of the Phase 2/3 DEVOTE study evaluating the safety and efficacy of an investigational higher dose regimen of nusinersen in spinal muscular atrophy (SMA), showing benefits in both individuals previously treated and treatment-naïve to nusinersen with infantile-onset or later-onset SMA. The investigational, higher dose regimen of nusinersen comprises a more rapid loading regimen, two 50 mg doses 14 days apart, and higher maintenance regimen, 28 mg, every 4 months, compared to the approved nusinersen regimen (SPINRAZA®). Data to be presented during the World Muscle Society (WMS) 2024 Congress (Oct. 8-12, 2024 in Prague) highlight the potential of this investigational higher dose regimen to help address remaining unmet need in SMA.
“Strikingly, the higher dose regimen lowered neurofilament more quickly, telling us that it’s more rapidly slowing neurodegeneration. We know how critical this is in people living with SMA. Over time, we see evidence of the benefit of the higher dose regimen across SMA phenotypes,” said Thomas Crawford, M.D., co-director, Muscular Dystrophy Association Clinic at Johns Hopkins Medicine. “Despite administering much more drug, the higher dose regimen appears to have a consistent safety profile with the approved 12 mg regimen.”
DEVOTE is a three-part study that enrolled 145 participants across ages and SMA types. The pivotal Part B cohort (n=75) met its primary endpoint where treatment-naïve, symptomatic infants who received the higher dose regimen saw significantly greater improvements in motor function as measured by Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND) compared to a prespecified matched sham (untreated) group from the Phase 3 ENDEAR study (+15.1 vs -11.1, p<0.0001).
Initial results were also presented from Part C (n=40) of DEVOTE, in which a diverse group of participants, age 4-65, transitioned to the higher dose regimen (one 50 mg dose followed by the 28 mg maintenance regimen) after a median of 3.9 years on the approved 12 mg regimen. Participants experienced improvements in motor function after transitioning with mean increases of 1.8 points on HFMSE and 1.2 points on RULM from baseline at Day 302.
Across parts of DEVOTE, the higher dose regimen was generally well tolerated and showed a safety profile similar to that of the approved 12 mg regimen. In the 12 mg regimen the most common adverse events (AEs) were respiratory infection, fever, constipation, headache, vomiting and back pain. The frequency of AEs in DEVOTE was similar across the nusinersen treatment arms. The number of AEs leading to study withdrawal and death only occurred in the Part B treatment-naive cohort and were 20% (10), 24% (6) and 55% (11), in the 50/28 mg, 12 mg and matched sham arms, respectively.
“While we’ve seen great progress over the past decade in improving the lives of those with SMA, gaps remain and we can do more to address the full range of unmet needs and goals within our community,” said Kenneth Hobby, President of Cure SMA. “The DEVOTE study’s findings are promising and show the potential for additional meaningful advancements that could further enhance motor function which impacts daily living activities for all people living with SMA.”
Biogen plans to file applications for the 50/28 mg higher dose nusinersen regimen with global regulatory agencies. Nusinersen is currently commercialized under the brand name SPINRAZA in over 71 countries at the label-approved dose of 12 mg.