Objective: 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/evaluate bulbar function in children with symptomatic SMA type 1 who received onasemnogene abeparvovec (OA).
Background: Improvement and maintenance of bulbar function is a goal of disease-modifying therapies in SMA. There is no widely accepted definition of bulbar function in SMA.
Methods: We defined bulbar function as 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.
Results: Overall, 65 patients aged <6 months at time of OA administration were analyzed. Sixty-five were analyzed for swallowing (START [n=11]; STR1VE-EU [n=32]; STR1VE-US [n=22]). 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 aspiration or pneumonia aspiration event reported. Overall, 80% (16/20) achieved the composite endpoint.
Conclusions: These post-hoc analyses indicate that symptomatic, type 1 SMA patients treated with onasemnogene abeparvovec could speak, swallow, and maintain airway protection, indicating they achieved good bulbar function.