FDA OKs Gene Therapy for Children with Spinal Muscular Atrophy


The drug, onasemnogene abeparvovec-xioi (Zolgensma, AveXis), is an adeno-associated virus vector-based gene therapy that targets the cause of SMA, a leading genetic cause of infant mortality.

Officials with the FDA have approved the first gene therapy for treating children less than 2 years of age with spinal muscular atrophy (SMA).

The drug, onasemnogene abeparvovec-xioi (Zolgensma, AveXis), is an adeno-associated virus vector-based gene therapy that targets the cause of SMA, a leading genetic cause of infant mortality.

The application for approval submitted by AveXis, a Novartis company, was granted the FDA's Fast Track, Breakthrough Therapy, and Priority Review designations, as well as an Orphan Drug designation. In addition, the FDA awarded AveXis a rare pediatric priority review voucher, under a program intended to encourage the development of new drugs and biological products for the prevention and treatment of certain rare pediatric diseases, according to the agency.

“Today’s approval marks another milestone in the transformational power of gene and cell therapies to treat a wide range of diseases,” said Acting FDA Commissioner Ned Sharpless, MD, in a prepared statement. “With each new approval, we see this exciting area of science continue to move beyond the concept phase into reality. The potential for gene therapy products to change the lives of those patients who may have faced a terminal condition, or worse, death, provides hope for the future. The FDA will continue to support the progress in this field by helping to expedite the development of products for unmet medical needs through the use of review pathways designed to advance innovative, safe and effective treatment options.”

Children with SMA have problems holding their head up, swallowing and breathing. These symptoms may be present at birth or may present by the age of 6 months.

“Children with SMA experience difficulty performing essential functions of life. Most children with this disease do not survive past early childhood due to respiratory failure” said Peter Marks, M.D., Ph.D., director of the FDA’s Center for Biologics Evaluation and Research. “Patients with SMA now have another treatment option to minimize the progression of SMA and improve survival. This approval demonstrates the continued momentum of this promising new area of medicine and the FDA’s commitment to supporting and helping expedite the development of these products.”

The safety and effectiveness of onasemnogene abeparvovec-xioi is based on an ongoing clinical trial and a completed clinical trial involving a total of 36 pediatric patients with infantile-onset SMA between the ages of approximately 2 weeks and 8 months at study entry, according to the FDA. The primary evidence of effectiveness is based on results from the 21 patients treated with Zolgensma in the ongoing clinical trial.

In this trial, there are 19 remaining patients, who range in age from 9.4 to 18.5 months; 13 of these 19 patients are at least 14 months of age. Compared to the natural history of patients with infantile-onset SMA, patients treated with Zolgensma also demonstrated significant improvement in their ability to reach developmental motor milestones (e.g., head control and the ability to sit without support).

"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 a prepared statement. "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 4 years out from the trial, and we see the durability of this gene therapy."

Vas Narasimhan, CEO of Novartis, said the approval of onasemnogene abeparvovec-xioi serves as a testament to the “transformational impact” that gene therapies can have in treating life-threatening genetic diseases, such as SMA.

"We believe Zolgensma could create a lifetime of possibilities for the children and families impacted by this devastating condition," Narasimhan added, in a prepared statement.

According to the FDA, a 1-time intravenous administration of onasemnogene abeparvovec-xioi results in expression of the SMN protein in a child’s motor neurons, which improves muscle movement and function, and survival of a child with SMA.

Dosing is determined based on the weight of the patient.

The most common adverse effects of onasemnogene abeparvovec-xioi are elevated liver enzymes and vomiting. The drug has a boxed warning that acute serious liver injury can occur, and patients with pre-existing liver impairment may be at higher risk of experiencing serious liver injury.

Clinical examination and laboratory tests to assess liver function should be completed prior to treatment with onasemnogene abeparvovec-xioi, and patients’ liver function should be monitored for at least 3 months after this drug is administered.

Certain vaccines are contraindicated for patients on a substantially immunosuppressive steroid dose. Health care professionals should offer consultation for determining potentially needed adjustments to patients’ vaccination schedules in order to accommodate concomitant corticosteroid administration.


  • FDA approves innovative gene therapy to treat pediatric patients with spinal muscular atrophy, a rare disease and leading genetic cause of infant mortality [news release]. Silver Spring, MD; May 24, 2019: FDA website. https://www.fda.gov/news-events/press-announcements/fda-approves-innovative-gene-therapy-treat-pediatric-patients-spinal-muscular-atrophy-rare-disease. Accessed May 24, 2019.
  • AveXis receives FDA approval for Zolgensma®, the first and only gene therapy for pediatric patients with spinal muscular atrophy (SMA) [news release]. Basel, Switzerland; May 24, 2019: AveXis website. http://investors.avexis.com/phoenix.zhtml?c=254285&p=irol-newsArticle&ID=2399684. Accessed May 24, 2019.

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