FP.23 Bulbar function for patients with spinal muscular atrophy type 1 following onasemnogene abeparvovec

Abstract

Spinal muscular atrophy (SMA) experts on deglutition, respiratory function, physical therapy, nutrition, and neurology, and Novartis gene therapies staff, conducted post-hoc analyses of pooled data from one Phase I (START) and two Phase III (STR1VE-US and STR1VE-EU) studies to define and evaluate bulbar function in children with symptomatic SMA type 1 who received onasemnogene abeparvovec. We defined bulbar function as the ability to orally communicate with comprehension by an unknown listener and swallow to orally meet nutritional needs while maintaining airway protection. We chose three endpoints to represent key components of bulbar function: (1) achievement of item #6 or above on the Bayley expressive communication subtest, (2) absence of clinician-identified (clinical or fluoroscopic) markers of physiologic swallowing impairment, and (3) absence of adverse events relating to respiratory health. We descriptively assessed numbers/percentages of patients who achieved each endpoint and all three. Patients were followed until 24 months of age in START and 18 months of age in STR1VE-EU and STR1VE-US. Overall, 65 patients were included. Sixty-five were analyzed for swallowing, nutrition, and respiratory compromise (START [n=11]; STR1VE-EU [n=32]; STR1VE-US [n=22]), and 20 were analyzed for the communication endpoint. Not all patients had outcomes for all three measures (START [n=4]; STR1VE-US [n=16]). At the end of the study, 95% (19/20) of patients met the communication endpoint, 92% (60/65) had evidence of a normal swallow, and 92% (60/65) had no respiratory adverse event reported. Overall, 80% (16/20) achieved the composite endpoint. Post-hoc analyses indicate that symptomatic SMA type 1 patients treated with onasemnogene abeparvovec could speak, swallow, and maintain airway protection, indicating they achieved good bulbar function.