Pharma Focus Asia

AveXis receives FDA approval for Zolgensma®, the first and only gene therapy for pediatric patients with spinal muscular atrophy (SMA)

Monday, May 27, 2019

AveXis, a Novartis company, today announced the US Food and Drug Administration (FDA) has approved Zolgensma® (onasemnogene abeparvovec-xioi) 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 a testament to the transformational impact gene therapies can have in reimagining the treatment of life-threatening genetic diseases like spinal muscular atrophy," said Vas Narasimhan, CEO of Novartis. "We believe Zolgensma could create a lifetime of possibilities for the children and families impacted by this devastating condition."

SMA is a rare, genetic neuromuscular disease caused by a defective or missing SMN1 gene. Without a functional SMN1 gene, infants with SMA lose the motor neurons responsible for muscle functions such as breathing, swallowing, speaking and walking.1 Left untreated, muscles become progressively weaker.1,2 In the most severe form, this eventually leads to paralysis and ultimately permanent ventilation or death by age 2 in more than 90% of cases.3 SMA is the leading cause of genetic infant death.4 Approximately 450 to 500 infants are born with SMA in the US annually.5,6 It is imperative to diagnose SMA and begin treatment, including proactive supportive care, as early as possible to halt irreversible motor neuron loss and disease progression.7 This is especially critical in the most severe form where degeneration starts shortly before birth and escalates quickly.8 With states adding SMA to their genetic newborn screening panel, babies with SMA can begin to be widely identified at birth and the ability to have earlier intervention can be improved.9

"Zolgensma's one-time dose of gene therapy has the potential to make a truly transformative impact on this life-threatening disease," said Kenneth Hobby, president of Cure SMA, a patient advocacy organization dedicated to the care, treatment and cure of SMA. "Our organization is leading the way to a world without SMA and we are excited the FDA's approval of Zolgensma brings patients and families a powerful new treatment which corrects the underlying cause of the disease."

The approval of Zolgensma is based on data from the ongoing Phase 3 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.

"We are grateful to the tenacious researchers, partners and families who participated in the Zolgensma clinical trials that helped us achieve this incredible milestone," said Dave Lennon, president of AveXis. "We are proud to bring this one-time gene therapy to pediatric patients with SMA and remain committed to advancing the science behind Zolgensma to transform SMA, as well as other rare genetic diseases."

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. This includes answering questions about Zolgensma, verifying reimbursement assistance and coordinating financial assistance programs for eligible patients. For more information, caregivers and healthcare professionals can call 1-855-441-GENE (1-855-441-4363).

Outside of the US, Zolgensma has PRIME (PRIority MEdicines) designation in Europe and is being reviewed under Accelerated Assessment Procedure, and also has accelerated Sakigake designation in Japan. In the interim, AveXis has arranged to make the product available for international markets, subject to local laws and regulations, as a part of its paid Managed Access Program via a collaboration with Durbin, a third-party provider. International inquiries regarding availability of Zolgensma outside of the US may be made by contacting Durbin at or +44-20-8869-6506.

AveXis has an exclusive, worldwide license with Nationwide Children's Hospital to both the intravenous and intrathecal delivery of AAV9 gene therapy for the treatment of all types of SMA; has an exclusive, worldwide license from REGENXBIO for any recombinant AAV vector in its intellectual property portfolio for the in vivo gene therapy treatment of SMA in humans; an exclusive, worldwide licensing agreement with Genethon for in vivo delivery of AAV9 vector into the central nervous system for the treatment of SMA; and a non‑exclusive, worldwide license agreement with AskBio for the use of its self‑complementary DNA technology for the treatment of SMA.

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