High Dose Spinraza Significantly Improves Motor Function in Infants with Spinal Muscular Atrophy

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Results from the Phase II/III DEVOTE trial found that when treated with a higher dose, Biogen’s Spinraza (nusinersen) produced significant motor function improvements in infants with spinal muscular atrophy (SMA) at six months compared to a matched untreated control group from the ENDEAR study. According to the company, the new regimen consists of two 50 mg doses 14 days apart and a 28 mg maintenance dose every four months.¹

“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, PharmD, head, neuromuscular development unit, Biogen, in a press release. “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.”

The randomized, controlled, dose-escalating DEVOTE trial was designed to evaluate the safety, tolerability, pharmacokinetics, and potential for even greater efficacy of Spinraza when administered at a higher dose compared to the currently approved 12 mg dose. Consisting of 145 patients across multiple SMA types, the Part B cohort included 75 treatment-naïve children with infantile-onset SMA. Patients in this cohort were randomly assigned at a ratio of 2:1 to receive the investigational higher dose regimen of Spinraza or the approved 12 mg dosing regimen. The primary endpoint was 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 ENDEAR study.

Results found a mean difference of 26.19 (p<0.0001), favoring the higher dose regimen compared to the untreated control group from the ENDEAR study. Additionally, results suggested that the higher dose of Spinraza has the potential to offer faster neurodegeneration slowdown and meaningful clinical benefits for infants with SMA.

The higher dose of Spinraza was found to be well tolerated, with adverse events (AEs) remaining consistent with the treatment’s known safety profile. Common AEs that were observed included respiratory infection, fever, constipation, headache, vomiting, and back pain. AEs were reported in 60% of patients in the high-dose cohort and 72% of those in the low-dose cohort.¹

According to The National Library of Medicine, SMA accounts for approximately 10 in every 100,000 births, with a recent study suggesting a range of 5.0 to 24 in 100,000 births. Prevalence of SMA is estimated to be approximately one to two in 100,000 people but is affected by the significantly shortened life expectancy in the most common type of SMA.²

“Although SMA is thought of as uncommon, it’s the second most common severe hereditary disease of infancy and childhood after cystic fibrosis,” reports the Cleveland Clinic. “Researchers estimate that it affects between 1 in 6,000 to 1 in 11,000 live births. SMA is about twice as common in white and Asian people as it is in Black and Hispanic people.”³

More detailed data from the DEVOTE study is expected to be shared at future medical conferences.¹

References

1. Biogen Announces Positive Topline Results from Study of Higher Dose Regimen of Nusinersen, Showing Significant Benefit in Treatment of SMA. Biogen. September 4, 2024. Accessed September 4, 2024. https://investors.biogen.com/news-releases/news-release-details/biogen-announces-positive-topline-results-study-higher-dose

2. Clinical Review Report: Nusinersen (Spinraza): (Biogen Canada Inc.): Indication: Treatment of patients with 5q SMA [Internet]. NIH. Accessed September 4, 2024. https://www.ncbi.nlm.nih.gov/books/NBK533981/

3. Spinal Muscular Atrophy (SMA). Cleveland Clinic. Accessed September 4, 2024. https://my.clevelandclinic.org/health/diseases/14505-spinal-muscular-atrophy-sma