The Food and Drug Administration (FDA) has approved onasemnogene abeparvovac-xioi (Zolgensma; Avexis, Bannockburn, IL) for the treatment of all types of spinal muscular atrophy (SMA) in children under age 2 years. Approved indications for onasemnogene, an SMN gene-replacement therapy, include all types of SMA. Treatment of presymptomatic children diagnosed through genetic screening is also approved. Not all states include testing for SMA in newborn screening panels, however.
Onasemnogene is given intravenously in a single 1-time infusion. In 2 clinical trials (STRIVE [NCT03306277] and STRONG [NCT03381729]. Of 36 children treated, 34 have survived without the need for ventilatory support (1 exited the early and 1 died from SMA at age 7.8 months). Of the 34 children remaining in the trial, all are achieving motor milestones not usually seen in children with SMA, including sitting, talking, and, for some, walking. Rapid motor function improvements were seen as early as 1 month after treatment, and no waning of effect has been seen over 4 years of treatment. Adverse effects included elevated liver transaminases, making liver function monitoring mandatory.
Untreated, SMA causes progressive motor degeneration leading to loss of motor function, need for continuous ventilation, and death in early childhood. The first treatment for SMA, nusinersen (Spinraza; Biogen, Cambridge, MA) was approved in 2016 and is given as quarterly intrathecal infusions.
Treatments for SMA are transformational and life-saving and also among the highest-priced of any drug therapy. Onasemnogene will be priced at $2.125 million per 1-time treatment. This price was set against and is 50% of the benchmarks of 10 years of nusinersen therapy, 10 years of treatment for genetic pediatric ultrarare diseases (estimated at $4.1 million), and the ultrarare disease cost-effectiveness threshold of $250,000 per quality-adjusted life-year (QALY).
Zolgensma has been manufactured and is available for use. The treatment will be marketed by AveXis, a Novartis company and their OneGene Program will provide comprehensive support to individuals and families affected by SMA to facilitate access to treatment.
Deena E. Kuruvilla, MD, FAHS
Michelle L. Dougherty, MD, FAES, FAAN