Novartis wins FDA approval for SMA gene replacement therapy

The U.S. FDA has approved Novartis’ Itvisma (onasemnogene abeparvovec-brve) for the treatment of children two years and older, teens and adults living with spinal muscular atrophy (SMA) with a confirmed mutation in the survival motor neuron 1 (SMN1) gene, making it the first and only gene replacement therapy available for a broad SMA population.

The approval is based on data from the registrational phase 3 STEER study and supported by the open-label phase 3b STRENGTH study, with Itvisma demonstrating statistically significant improvements in motor function and stabilization of motor abilities typically not seen in the natural history of the disease, with effects sustained over 52 weeks of follow-up.

Itvisma is an intrathecal formulation of Novartis’ Zolgensma — a gene therapy approved in 2019 for infants with SMA — enabling gene replacement therapy to be delivered safely and effectively to older children, teens and adults for the first time. Zolgensma is administered intravenously based on patient weight, while Itvisma is a concentrated formulation in a smaller delivery volume, administered directly to the central nervous system via a single intrathecal injection independent of patient weight.

SMA is a rare, genetic neuromuscular disease caused by a mutated or missing SMN1 gene, which is responsible for producing most of the SMN protein a body needs for muscle function, including breathing, swallowing and basic movement. Itvisma is designed to address the genetic root cause of SMA with a one-time fixed dose that does not need to be adjusted for age or body weight. By replacing the SMN1 gene, Itvisma can improve motor function, offering the potential to reduce the need for chronically administered treatment associated with other available therapies for this population.