Single Dose of Onasemnogene Abeparvovec Provides Sustained Efficacy for SMA

A 5-year follow-up of the phase 1 START trial of infants with spinal muscular atrophy (SMA) type 1 revealed no new safety concerns or treatment-related serious adverse events for onasemnogene abeparvovec gene replacement therapy. Researchers published results online ahead of print in JAMA Neurology.

“Onasemnogene abeparvovec, at the therapeutic dose, maintained a durable response in patients up to 5.6 years after dosing, as of the June 11, 2020, data cutoff, which is unmatched in the natural history of patients with SMA,” wrote researchers. “All 10 patients in the therapeutic-dose cohort and 2 of the 3 patients in the low-dose cohort were alive and did not require permanent ventilation at the time of this analysis.” 

The follow-up included 13 of 15 children with symptomatic SMA type 1 treated as infants with a single intravenous low or therapeutic dose (the latter of which became the approved dose) of onasemnogene abeparvovec in the START study at Nationwide Children’s Hospital. Two patients’ families from the original study declined participation in the extension study. 

Over follow-up, 62% of the 13 patients experienced serious adverse events, the study found. The most frequently reported were acute respiratory failure (31%), pneumonia (31%), dehydration (23%), respiratory distress (15%), and bronchiolitis (15%). None resulted in study discontinuation or death.

Among the 10 patients who received the therapeutic dose, all maintained previously acquired motor milestones, researchers reported. Two even achieved the “standing with assistance” milestone without the use of nusinersen.    

“Onasemnogene abeparvovec provides sustained and durable efficacy in patients up to 6.2 years after dosing. Anticipated results from completed and ongoing phase 3 and 4 studies will further confirm the efficacy and safety of onasemnogene abeparvovec,” researchers wrote. “Current evidence demonstrates that onasemnogene abeparvovec continues to have a favorable benefit-risk profile for the treatment of pediatric patients with SMA.”

Reference:

Mendell JR, Al-Zaidy SA, Lehman KJ, et al. Five-Year Extension Results of the Phase 1 START Trial of Onasemnogene Abeparvovec in Spinal Muscular Atrophy [published online ahead of print, 2021 May 17]. JAMA Neurol. 2021;e211272. doi:10.1001/jamaneurol.2021.1272