FDA Approves First-of-Its-Kind Gene Therapy
On May 24, 2019, Zolgensma became the first gene therapy approved by the U.S. Food and Drug Administration (FDA) for spinal muscular atrophy. It is the second gene therapy approved in the United States.
SMA, the number one genetic killer of babies under two years of age, is a progressive, childhood, neuromuscular disease caused by a mutation in a single gene. Children with SMA type 1 fail to meet motor milestones and typically die or require permanent mechanical ventilation by 2 years of age.
Jerry Mendell, MD, and Evelyn Villarreal, one of the clinical trial participants with SMA type 1 who received the new gene therapy
Jerry Mendell, MD, principal investigator in the Center for Gene Therapy at the Abigail Wexner Research Institute led the Phase 1 clinical trial to study gene therapy for SMA1. In the trial, an intravenous injection of Zolgensma delivered a functional copy of the gene to the participants’ cells.
Most children in the study who received the FDA-approved dose gained the ability to sit and roll, and a few could crawl or walk. Additionally, after two years, 7 of 10 participants who were free of pulmonary support at the time of dosing remained support-free.
“Treatment of SMA1 with gene therapy has the potential to transform the disease course, in addition to improving patient and caregiver quality of life. Reduced used of ventilation and nutritional support, as well as decreased hospitalization, could significantly decrease the overall health care utilization of these patients,” says Richard Shell, MD, section chief of Pulmonary Medicine at Nationwide Children’s and senior author of the publication describing long-term health outcomes of the therapy.
The preclinical work leading to the FDA approval of Zolgensma was conducted by researchers from Nationwide Children’s and The Ohio State University College of Medicine. The therapy was licensed to AveXis to help advance its use into the clinical setting.
“Our Center for Gene Therapy is a national leader in gene therapy with a robust pipeline of more than 20 genetic targets in various stages of research,” says Kevin Flanigan, MD, director of the Center for Gene Therapy. “The Abigail Wexner Research Institute invested in a clinical trial infrastructure, a Good Manufacturing Practice facility, regulatory experts and an Office of Technology Commercialization with the goal of taking discoveries from the laboratory bench to the clinic.”
CITATION:
Al-Zaidy S, Pickard AS, Kotha K, Alfano LN, Lowes L, Paul G, Church K, Lehman K, Sproule DM, Dabbours O, Maru B, Berry K, Arnold WD, Kissel JT, Mendell JR, Shell R. Health Outcomes in Spinal Muscular Atrophy Type 1 Following AVXS-101 Gene Replacement Therapy. Pediatric Pulmonology. 2019;54:179-185.
Mendell JR, Al-Zaidy S, Shell R, Arnold WD, Rodino-Klapac LR, Prior TW, Lowes L, Alfano L, Berry K, Church K, Kissel JT, Nagendran S, et al. Single-Dose Gene-Replacement Therapy for Spinal Muscular Atrophy. The New England Journal of Medicine. 2017 Nov 2;377:1713-1722.
