Biogen Reports Positive Results from Higher Dose Nusinersen Study for SMA Treatment

Biogen Inc. has announced promising topline results from Part B of the Phase 2/3 DEVOTE study, which investigates the safety and efficacy of a higher dose regimen of nusinersen in infants newly diagnosed with spinal muscular atrophy (SMA). The new dosing regimen includes an accelerated loading phase with two 50 mg doses spaced 14 days apart, followed by a 28 mg maintenance dose every four months. This is a significant increase compared to the current approved nusinersen regimen, known as SPINRAZA, which consists of 12 mg doses.

At the six-month mark, the study achieved its primary goal by showing a statistically significant improvement in motor function for infants on the higher dose regimen compared to a matched control group of untreated infants from the ENDEAR study. Stephanie Fradette, Head of the Neuromuscular Development Unit at Biogen, highlighted that these results build on SPINRAZA’s established safety profile over the past decade. The higher dose regimen of nusinersen was shown to slow neurodegeneration more rapidly and provide meaningful clinical benefits over time.

The DEVOTE study is divided into three parts and includes 145 patients from various age groups and SMA types. Part B, which is pivotal, consisted of treatment-naïve children with infantile-onset SMA. These children were randomly assigned in a 2:1 ratio to receive either the higher dose regimen or the approved 12 mg regimen. The primary efficacy endpoint was the change from baseline on the Children's Hospital of Philadelphia-Infant Test of Neuromuscular Disorders (CHOP-INTEND) at six months, comparing the investigational dose to a matched control group from the ENDEAR study.

The findings revealed that the higher dose regimen led to a significant improvement in CHOP-INTEND scores from baseline to six months, showing a least squares mean difference of 26.19 (p<0.0001) compared to the sham control group. Additionally, the higher dose regimen demonstrated favorable outcomes across various secondary endpoints and showed trends of superiority over the approved 12 mg dose in key biomarker and efficacy measures. The safety profile of the higher dose regimen was consistent with known nusinersen safety data and the nature of SMA, with fewer serious adverse events reported compared to the 12 mg group.

The DEVOTE study not only aims to prove the enhanced efficacy and safety of a higher nusinersen dose but also to transition patients from the current approved dose to this new regimen. This includes an open-label safety evaluation cohort and continued assessments for long-term safety and tolerability.

SPINRAZA, approved in over 71 countries, has treated more than 14,000 individuals worldwide, making it a cornerstone in SMA care. It is designed as an antisense oligonucleotide (ASO) that addresses motor neuron loss by boosting the production of full-length survival motor neuron (SMN) protein within the central nervous system. With a robust safety profile documented over a decade and extensive real-world experience, SPINRAZA remains a critical treatment option for SMA patients.

Biogen, founded in 1978, continues to lead in biotechnology by developing innovative medicines aimed at transforming patient lives and delivering value to shareholders and communities. The company’s efforts in advancing SMA treatments highlight its commitment to pioneering new scientific solutions for unmet medical needs.