The United States FDA has approved Zolgensma (AveXis) for the treatment of spinal muscular atrophy (SMA) in pediatric patients <2 years of age with mutations in the SMN1 gene.1 Zolgensma is the first and only gene therapy FDA-approved for SMA, including patients who are presymptomatic.

"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 statement.2 "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.”

Phase 1 START trial results for Zolgensma, an adeno-associated virus vector-based, one-time gene therapy administered via intravenous infusion, demonstrated motor milestones never before seen in the natural history of the disease, including sitting, talking, and walking in some patients. Notably, no waning effects were observed 4 years post-dose.

The approval is based on data from the ongoing phase 3 STR1VE trial as well as the phase 1 START trial, which included patients with SMA type 1 who showed symptoms at <6 months. Patients enrolled in STR1VE have shown prolonged event-free survival, motor function increase, and ongoing milestone achievement as observed in START.

Additional phase 3 data from the open-label SPR1NT trial in patients ≤6 weeks of age, which were presented at the 2019 American Academy of Neurology Annual Meeting, demonstrated ongoing event-free survival in patients with 2 copies of SMN2 (n = 8), as well as a mean improvement of 8.9 points in Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND) at 1 month, with all patients achieving or maintaining a CHOP-INTEND score of ≥50 points, 6 patients achieving CHOP-INTEND scores of 60 points, and 3 achieving the maximum score of 64 points.

In addition, Bayley-III Gross Motor scores were an average of 8.4 at 2 months post-infusion, with 4 patients able to sit without support for ≥30 seconds, and a single patient able to stand with assistance for ≥2 seconds. Across all trials, the most commonly observed adverse events were elevated aminotransferases and vomiting.

Novartis, the parent company of AveXis, has announced access programs for Zolgensma, of which a single dose will be priced at $2.125 million. AveXis is reportedly working closely with payers to offer pay-over-time options and affordability and access programs aimed at patients.3
REFERENCES:
1. AveXis receives FDA approval for Zolgensma®, the first and only gene therapy for pediatric patients with spinal muscular atrophy (SMA) [news release]. Basel, Switzerland: Novartis. May 24, 2019.
2. 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]. US FDA. May 24 2019. fda.gov/news-events/press-announcements/fda-approves-innovative-gene-therapy-treat-pediatric-patients-spinal-muscular-atrophy-rare-disease

3. AveXis announces innovative Zolgensma® gene therapy access programs for us payers and families [news release]. Basel, Switzerland: Novartis. May 24, 2019.