Early Presymptomatic Treatment With Nusinersen Results Show Continued Increases in Meeting Motor Milestones
Results from the NURTURE study (NCT02386553) show presymptomatic infants with spinal muscular atrophy (SMA) treated with nusinersen (Spinraza; Biogen, Cambridge MA) for up to 5.7 years (median 4.9 years) continue gaining motor function. To date, 23 of 25 participants (92%) can walk independently, and most (88%) have reached the maximum score on the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND) scale.
No participants have lost motor milestones, and only a small number (4/25, 16%) have needed temporary respiratory support during acute illnesses, with only 3 (12%) still doing so. The individuals who required such support all had fewer copies of the survival of motor neuron 2 (SMN2) gene; nusinersen acts on transcripts of this gene. No participants have left the study or discontinued treatment.
Maha Radhakrishnan, MD, chief medical officer at Biogen said, “Spinraza has demonstrated significant benefit in individuals with SMA, from presymptomatic infants to adults with later-onset SMA. Additionally, the latest results from the landmark NURTURE study continue to show that most infants who began treatment with Spinraza before the clinical onset of symptoms achieved motor milestones in timeframes consistent with normal development.”
Nusinersen is also being evaluated for use in people who have had other treatments for SMA. Children with SMA are eligible to participate in the RESPOND trial (NCT04488133) if they have suboptimal response in motor function, need for respiratory support, or dysphagia after treatment with onasemnogene (Zolgensma; Novartis, East Hanover, NJ). Of the 9 participants treated to date, all had suboptimal response to onasemnogene in 2 or more domains; no new safety signals were observed.
The ASCEND study (NCT05067790) will examine effects of nusinersen in children, adolescents, and adults previously with risdiplam (Evrysdi; Genentech, South San Francisco, CA). Novel aspects of this study are use of the Revised Upper Limb Module (RULM) score as a primary endpoint and self-assessment of motor function in daily activities, via a smartphone-based application (Konectom NMD; Biogen Digital Health), as an exploratory endpoint.
“As the SMA community gains more experience with available therapies, we are gleaning new insights about how these treatments can enhance the lives of individuals impacted by SMA. However, unmet needs still remain for the community,” said Basil Darras, MD, professor of Neurology at Harvard Medical School and director of the Neuromuscular Center and Spinal Muscular Atrophy Program at Boston Children's Hospital. “The ASCEND study seeks to generate data that have the potential to inform decisions regarding treatment for our patients with later-onset SMA.”