Biogen has reported positive topline results from the Part B cohort of the Phase 2/3 DEVOTE study of an increased dose regimen of Spinraza (nusinersen) in treatment-naïve, symptomatic infants with spinal muscular atrophy (SMA).
Spinraza, approved in over 71 countries, treats SMA by increasing full-length survival motor neuron (SMN) protein.
Biogen holds the global rights to develop, manufacture, and commercialise Spinraza, which it acquired from Ionis Pharmaceuticals.
Nusinersen received the US Food and Drug Administration (FDA) approval in 2016.
The new regimen features a more rapid loading phase. It consists of two 50mg doses given 14 days apart and a higher maintenance dose of 28mg every four months, compared to the currently approved nusinersen regimen.
The DEVOTE study is a comprehensive three-part trial that enrolled 145 patients spanning various ages and SMA types.
The Part B cohort included 75 treatment-naïve infants with infantile-onset SMA, who were randomised in a 2:1 ratio to receive either the investigational higher dose regimen of nusinersen or the approved 12mg regimen.
The study achieved its primary endpoint at six months.
It showed a statistically significant improvement in motor function in infants treated with the higher dose regimen compared to a matched sham control group from the ENDEAR study.
ENDEAR is one of the two studies that supported the regulatory approval of Spinraza at 12mg.
The higher dose cohort demonstrated a statistically significant improvement compared to the matched sham comparator on the primary endpoint, which was the change in CHOP-INTEND scores from baseline to six months.
This regimen also showed favourable results across secondary endpoints and trended positively compared to the currently approved 12mg regimen in key biomarker and efficacy measures.
The higher dose regimen was generally well tolerated, with adverse events aligning with the typical profile for SMA and nusinersen.
Biogen neuromuscular development unit head Stephanie Fradette said: “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.”
In 2022, Biogen obtained an exclusive global licence from Ionis Pharmaceuticals for the latter’s potential SMA treatment, BIIB115.
