Biogen's Spinraza (nusinersen) has shown promising results in a Phase II/III clinical trial, DEVOTE, utilizing a higher dosage regimen for infants with spinal muscular atrophy (SMA). The trial demonstrated statistically significant improvements in motor function compared to a sham control group, potentially paving the way for regulatory approval and altering treatment frameworks for SMA.
The DEVOTE trial (NCT04089566) enrolled 145 patients across various ages and SMA types, with Part B focusing on 75 treatment-naïve infants with infantile-onset SMA. Participants were randomized in a 2:1 ratio to receive either the experimental higher dose or the FDA-approved dose of nusinersen. The experimental higher dose included a loading regimen of two 50-mg doses administered 14 days apart, followed by maintenance doses of 28 mg every four months. This contrasts with the FDA-approved regimen of four 12-mg loading doses and 12-mg maintenance doses every four months.
Significant Improvement in Motor Function
The primary endpoint of DEVOTE was the change from baseline in the Children's Hospital of Philadelphia-Infant Test of Neuromuscular Disorders (CHOP-INTEND) score at 6 months post-treatment. The higher dose regimen demonstrated a statistically significant improvement compared to the sham treatment group, with a least squares mean difference of 26.19 (P < .0001). Secondary endpoints also favored the experimental dose regimen, with key biomarker and efficacy measures trending positively compared to the FDA-approved regimen.
Stephanie Fradette, PharmD, head of the Neuromuscular Development Unit at Biogen, stated, "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."
Safety and Tolerability
The experimental dose regimen was generally well-tolerated, with adverse events (AEs) consistent with the established safety profile of nusinersen and the disease itself. Notably, 60% of patients receiving the experimental dose in Part B experienced serious AEs (SAEs), compared to 72% in the FDA-approved dose group.
Context and Future Directions
Spinraza, an antisense oligonucleotide (ASO), addresses the root cause of motor neuron loss by increasing the production of survival motor neuron (SMN) protein. It is approved in over 71 countries for treating SMA in infants, children, and adults. Despite its success, Biogen aims to maximize efficacy outcomes while maintaining a commitment to safety, as stated by Fradette.
Biogen plans to pursue regulatory approval for this investigational dose regimen. Further details from the DEVOTE trial will be presented at upcoming medical conferences. This development could reshape existing therapeutic approaches and maintain Biogen's competitive edge in the evolving pharmaceutical landscape.
