Gene Therapy Improves Survival for Infantile Spinal Muscular Atrophy

Onasemnogene abeparvovec yielded clinically meaningful responses and a favorable benefit-risk profile for patients with spinal muscular atrophy type 1, according to findings from a recent phase 3 trial.

“Spinal muscular atrophy type 1 is a motor neuron disorder resulting in death or the need for permanent ventilation by age 2 years,” wrote Prof John W Day, MD, and colleagues on the importance of the STR1VE trial.

Investigators sought to evaluate the safety and efficacy of a gene therapy, onasemnogene abeparvovec, to deliver the survival motor neuron gene (SMN) in patients with infantile-onset spinal muscular atrophy.

The open-label, single-arm, single-dose phase 3 STR1VE trial was conducted across 12 locations in the United States.

To be eligible, patients had to be younger than 6 months and have spinal muscular atrophy with biallelic SMN1 mutations and one or two copies of SMN2.

A total of 22 patients with spinal muscular atrophy type 1 were eligible and included in the study from October 2017 to November 2019 to receive onasemnogene abeparvovec.

The coprimary efficacy endpoints were independent sitting for 30 seconds or longer at the 18 month of age study visit and survival at age 14 months.

Primary endpoints for the intention-to-treat population were compared with untreated infants 6 months or younger with spinal muscular atrophy type 1 from the Pediatric Neuromuscular Clinical Research dataset.

At the 18 month of age study visit, 59% of patients (n=13 of 22) had achieved functional independent sitting for 30 seconds or longer compared to 0% (n=0 of 23) of the untreated PNCR cohort.

20 patients (91%) treated with onasemnogene abeparvovec survived free from permanent ventilation at age 14 months versus 6 (23%) in the untreated PNCR cohort.

All patients experienced at least one adverse event; pyrexia was the most common. The most frequently reported serious adverse events were bronchiolitis, pneumonia, respiratory distress and respiratory syncytial virus bronchiolitis.

Overall, onasemnogene abeparvovec yielded clinically meaningful responses and statistical superiority compared with observations from the PNCR natural history cohort. Investigators noted these results build on findings from the phase 1 START trial to show the efficacy and safety of onsemnogene abeparvovec.

“The favourable benefit–risk profile shown in this study supports the use of onasemnogene abeparvovec for treatment of symptomatic patients with genetic or clinical characteristics predictive of infantile-onset spinal muscular atrophy type 1,” Dr Day et al concluded.—Kaitlyn Manasterski