FDA approves Zolgensma to treat spinal muscular atrophy.

AveXis, a Novartis company, announced that the FDA has approved Zolgensma (onasemnogene abeparvovac-xioi), one-time dose of gene therapy , for the treatment of pediatric patients less than 2 years of age with spinal muscular atrophy (SMA) with bi-allelic mutations in the survival motor neuron 1 (SMN1) gene. Zolgensma is designed to address the genetic root cause of SMA by providing a functional copy of the human SMN gene to halt disease progression through sustained SMN protein expression with a single, one-time intravenous (IV) infusion. Zolgensma is the first and only gene therapy approved by the FDA for the treatment of SMA, including those who are pre-symptomatic at diagnosis.

"A diagnosis of SMA is devastating, leaving untreated babies who have the most severe form with painfully short, highly medicalized lives, during which they are unable to lift their heads, sit or roll, have difficulty swallowing and breathing and need 24-hour care," said Jerry Mendell, M.D., principal investigator at the Center for Gene Therapy at The Abigail Wexner Research Institute of Nationwide Children's Hospital in Columbus, OH. "In the START clinical trial we conducted with Zolgensma, all children were alive at the conclusion of the study and many were able to sit, roll, crawl, play and some could walk. This level of efficacy, delivered as a single, one-time therapy, is truly remarkable and provides a level of unprecedented hope for families battling SMA Type 1. We now have data four years out from the trial, and we see the durability of this gene therapy."

The approval of Zolgensma is based on data from the ongoing Phase III STR1VE trial and the completed Phase 1 START trial evaluating the efficacy and safety of a one-time IV infusion of Zolgensma in patients with SMA Type 1 who showed symptoms of SMA at <6 months of age, with one or two copies in the STR1VE trial or two copies in the START trial of the SMN2 backup gene and who have bi-allelic SMN1 gene deletion or point mutations. These data show Zolgensma provides unprecedented rates of survival never seen in the natural history of the disease; rapid motor function improvement, often within one month of dosing; and, durable milestone achievement, including the ability to sit without support, a milestone never achieved in untreated patients. Safety observations in STR1VE were comparable to those seen in the START trial. The most commonly observed adverse events were elevated aminotransferases and vomiting..

Zolgensma will be made available in the US and will be marketed by AveXis, a Novartis company. OneGene Program, AveXis' comprehensive patient support program, provides a dedicated, personalized support team focused on the needs of each family throughout the Zolgensma treatment journey.

Comment: Zolgensma has PRIME (PRIority MEdicines) designation in Europe and is being reviewed under Accelerated Assessment Procedure, and also has accelerated Sakigake designation in Japan.