Bulbar Function in Children with Two or Three SMN2 Copies Who Received Onasemnogene Abeparvovec Presymptomatically for Spinal Muscular Atrophy
Katlyn McGrattan1, Richard Shell2, Rebecca Hurst-Davis3, Sally Dunaway Young4, Giovanni Baranello5, Arseniy Lavrov6, Eamonn O'Brien7, Shiri Wallach6, Nicole LaMarca6, Sandra P. Reyna6, Basil Darras8
1University of Minnesota, 2Nationwide Children’s Hospital and Department of Pediatrics, The Ohio State University, 3Primary Children’s Hospital, 4Stanford University School of Medicine, 5The Dubowitz Neuromuscular Centre, Developmental Neuroscience Research and Teaching Department, UCL Great Ormond Street Institute of Child Health and NIHR Great Ormond Street Hospital Biomedical Research Centre & Great Ormond Street Hospital NHS Foundation Trust, 6Novartis Gene Therapies, Inc., 7Novartis, 8Boston Children’s Hospital, Harvard Medical School
Objective:
We conducted a post-hoc analysis on bulbar function from a Phase III study (SPR1NT) of presymptomatic children with spinal muscular atrophy (SMA) with two (n=14) or three copies (n=15) of the SMN2 gene who received onasemnogene abeparvovec.
Background:
A goal of disease-modifying treatment for SMA is the improvement and maintenance of bulbar function, but there are no standardized and validated measures, and no widely accepted definition of bulbar function in SMA exists.
Design/Methods:
A group of experts on deglutition, respiratory function, physical therapy, nutrition, and neurology, and Novartis Gene Therapies staff defined bulbar function as the ability to establish verbal communication skills and to swallow to orally meet nutritional needs and maintain airway protection. Four endpoints were selected to represent key components of bulbar function: (1) achievement of item #6 or above on the Bayley Expressive Communication subtest, (2) receiving full oral nutrition, (3) absence of clinician-identified (clinical/fluoroscopic) markers of physiologic swallowing impairment, and (4) absence of adverse events relating to respiratory health (aspiration/aspiration pneumonia). Because communication skills were not assessed during SPR1NT, numbers/percentages of children who achieved each of the three available endpoints and all three endpoints (composite endpoint) were descriptively assessed. Last follow-up was at 18 and 24 months of age for children with two and three SMN2 copies, respectively.
Results:
Twenty-nine children were included in the analyses of three outcomes pertaining to bulbar function. At end of study, 100% (29/29) received full oral nutrition, 100% (29/29) had evidence of a normal swallow, and 100% (29/29) had no respiratory adverse events related to aspiration; 100% (29/29) met the composite endpoint.
Conclusions:
Presymptomatic children with SMA treated with onasemnogene abeparvovec could swallow, meet oral nutritional needs, and maintain airway protection, indicating they achieved good bulbar function and achieved motor milestones consistent with typically developing children.