FDA Approves Novartis’ Gene Replacement Therapy for SMA

Rare Daily Staff

The U.S. Food and Drug Administration has approved Novartis’ gene replacement therapy Itvisma for the treatment of children 2 years and older, teens, and adults living with spinal muscular atrophy (SMA) with a confirmed mutation in the survival motor neuron 1 (SMN1) gene.

It is the first and only gene replacement therapy available for this broad population.

Itvisma (onasemnogene abeparvovec) 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, potentially reducing the need for chronic treatment associated with other available therapies for this population.

SMA is a rare genetic neuromuscular disease caused by a mutation or deletion of the SMN1 gene. The SMN1 gene produces most of the SMN protein a body needs for muscle function, including breathing, swallowing, and basic movement. Without it, motor neurons are irreversibly lost, leading to progressive, debilitating muscle weakness. A second gene, SMN2, produces about 10 percent of the functional SMN protein compared with SMN1. Individuals with more copies of the SMN2 gene generally have a less severe form of SMA than those with fewer copies.

Itvisma is designed to address the genetic root cause of SMA by providing a functional copy of the human SMN1 gene to improve motor function through sustained SMN protein expression with a single, one-time intrathecal injection.

The FDA’s approval of Itvisma is based on data from the registrational Phase 3 STEER study, supported by the open-label Phase 3b STRENGTH study. Itvisma showed 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 also demonstrated a safety profile with adverse events consistent across both studies.

The most common adverse events in the STEER study were upper respiratory tract infection and pyrexia. In the STRENGTH study, the most common events were common cold, pyrexia, and vomiting.

Novartis holds an exclusive, worldwide license with Nationwide Children’s Hospital for both intravenous and intrathecal delivery of adeno-associated virus 9 (AAV9) gene replacement therapy for the treatment of all types of SMA. The company also has an exclusive, worldwide license from REGENXBIO for any recombinant AAV vector in its intellectual property portfolio for in vivo gene replacement therapy treatment of SMA in humans, as well as an exclusive, worldwide licensing agreement with Généthon for in vivo delivery of AAV9 vector into the central nervous system for the treatment of SMA.

“The FDA’s approval of intrathecal onasemnogene abeparvovec is a game-changing advance, expanding the use of transformational gene replacement therapy for SMA across age groups,” said John Day, professor of neurology and pediatrics, director of the Division of Neuromuscular Medicine at Stanford University School of Medicine, and co-director of Stanford’s Neuro IGNITE Center. “This achievement is not only a significant step forward for SMA, but it also signals new possibilities for the broader field of neurological disorders and genetic medicine.”