Bulbar Function in Children with Two or Three SMN2 Copies Who Received Onasemnogene Abeparvovec Presymptomatically for Spinal Muscular Atrophy


Clinical Trials

Poster Number: 155


Katlyn McGrattan, University of Minnesota, Richard Shell, MD, Nationwide Children's Hospital, Rebecca Hurst-Davis, Primary Children's Hospital, Sally Dunaway Young, PT, DPT, Stanford University, Giovanni Baranello, MD, Great Ormond Street Hospital for Children, Arseniy Lavrov, PhD, Novartis Gene Therapies, Inc., Eamonn O'Brien, Novartis, Shiri Wallach, PhD, Novartis Gene Therapies, Nicole LaMarca, DNP, MSN, CPNP, Novartis Gene Therapies, Inc., Sandra Reyna Merida, M.D., Novartis Gene Therapies, Basil Darras, MD, Department of Neurology, University of Pittsburgh, Pittsburgh, PA

Background: A goal of disease-modifying treatment for spinal muscular atrophy (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.
Objective: We conducted a post-hoc analysis on bulbar function from a Phase III study (SPR1NT) of presymptomatic children with SMA with two (n=14) or three copies (n=15) of the SMN2 gene who received onasemnogene abeparvovec.
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.