New trial data demonstrate age-appropriate development and achievement of motor milestones in presymptomatic children with SMA using single-agent gene therapy, without any respiratory or nutritional support or serious treatment-related adverse events.
If left untreated, spinal muscular atrophy (SMA) type 1 often leads to death or the need for permanent ventilation by the age of two. The SPR1NT study included children with two SMN2 copies presymptomatic. They received the only single-agent causal gene therapy to date, onasemnogen abeparvovec (Zolgensma®). The results demonstrate that all children were alive, free of ventilatory and nutritional support, and met the primary end point of sitting independently for ≥30 seconds. 11 of the 14 patients (78.6%) reached this milestone within the WHO-defined period of expected normal development. In addition, 11 of the 14 patients were subsequently able to stand independently and 9 of 14 were even able to walk independently. Most patients reached these milestones within the normal period of age-appropriate development.
The STR1VE-EU study evaluated the efficacy and safety of a single, one-time i.v. infusion of Zolgensma® in patients with SMA type 1 and a biallelic deletion in the SMN1 gene or point mutations and one or two copies of the SMN2 gene. Of the 33 patients included, nine (27%) required nutritional support at baseline, another nine (27%) required ventilatory support at baseline, and five (15%) required both. It was found that with therapy, the majority of symptomatic patients with SMA type 1 (82%), including those with a more severe course of SMA, achieved milestones of motor development not previously observed in the natural history of SMA type 1. Sixteen of these children (49%) were even able to sit independently for ≥30 seconds. The exploratory endpoint, “ability to develop in an age-appropriate manner” in symptomatic patients, including swallowing, oral feeding, and age-appropriate weight maintenance, was also evaluated. Twenty-three patients belonged to the ‘ability to thrive’ population, of whom seven patients (30%) met the criteria at 18 months of age.
Source: New data on Zolgensma® show age-appropriate progression in presymptomatic patients and rapid, clinically meaningful efficacy in symptomatic patients, including those with severe SMA at baseline, Jun. 23, 2021, Novartis
InFo NEUROLOGY & PSYCHIATRY 2021; 19(4): 33.
