Onasemnogene abeparvovec is efficacious in infants with symptomatic spinal muscular atrophy (SMA) type 1, according to the results of the phase 3 STRIVE-EU study that were published in The Lancet Neurology.
The researchers identified no new safety signals but said more research is needed to evaluate the long-term safety of the treatment.
The aim of the STRIVE-EU study was to evaluate the safety and efficacy of onasemnogene abeparvovec in infants with SMA type 1 using broader eligibility criteria than those used in the STRIVE-US study, meaning that patients with more severe disease were included in the study.
It was an open-label, single-arm, single-dose trial in patients with SMA type 1 aged less than 180 days (6 months) with a biallelic pathogenic mutation in the survival motor neuron 1 (SMN1) gene and 1 or 2 copies of the survival motor neuron 2 (SMN2) gene.
The primary outcome measure was the number of participants who achieved independent sitting for at least 10 seconds, something patients with SMA type 1 can rarely do. The secondary outcome measure was event-free survival at 14 months. An event was defined as death, the need for permanent ventilation, or withdrawal from the study.
Read more about SMA therapies
The trial assessed 41 patients for eligibility between August 16, 2018, and September 11, 2020, 33 of whom completed the study. One patient was excluded from the analysis because they received their treatment when they were 181 days old. The participants were given a single intravenous infusion of onasemnogene abeparvovec, and they were assessed once a week for 4 weeks starting at day 7 after the infusion and then once per month until the end of the study, when patients reached the age of 18 months.
The results showed that all 32 participants reached the primary endpoint. Only 1 patient (2%) required permanent ventilation at 14 months; this number was 6 out of 23 (26%) in the natural history cohort.
The results also showed that 32 patients had at least 1 adverse event. The most common of these were pyrexia, upper respiratory infections, and increased alanine aminotransferase. Six patients had serious adverse events related to the treatment. One patient died from hypoxic-ischemic brain damage due to a respiratory tract infection.
Onasemnogene abeparvovec is a gene replacement therapy that delivers a healthy copy of the SMN1 gene to the body, which is mutated in SMA. It was approved by the US Food and Drug Administration (FDA) in May 2019 under the brand name Zolgensma® and received conditional approval from the European Medicines Agency (EMA) in May 2020.
Mercuri E, Muntoni F, Baranello G, et al.; STR1VE-EU Study Group. Onasemnogene abeparvovec gene therapy for symptomatic infantile-onset spinal muscular atrophy type 1 (STR1VE-EU): an open-label, single-arm, multicentre, phase 3 trial. Lancet Neurol. 2021;20(10):832-841. doi:10.1016/S1474-4422(21)00251-9
Single-dose gene replacement therapy clinical trial for participants with spinal muscular atrophy type 1 (STRIVE-EU). ClinicalTrials.gov. March 12, 2018. Updated April 14, 2021. Accessed September 24, 2021.