AveXis announced interim long-term follow-up data from the Phase 1 trial of Zolgensma that showed durability of the one-shot gene therapy in patients with spinal muscular atrophy (SMA) Type 1 nearly four years after treatment. This data was presented during the 2019 American Academy of Neurology (AAN) Conference.
Zolgensma is designed to address the genetic root cause of SMA and prevent further muscle degeneration by providing a functional copy of the human SMN gene to halt disease progression through sustained SMN protein expression. The therapy represents the first in treating rare, monogenic diseases using gene therapy.
“As someone who has worked with SMA Type 1 patients for more than five decades and witnessed the devastation the disease has on families, it is truly remarkable to now be able to watch these babies grow up and become children living functional lives,” said Jerry Mendell, M.D., Center for Gene Therapy at Nationwide Children’s Hospital. “At the time we began the START study, most babies with SMA Type 1 would die or require permanent ventilation before age two. Now with four years of data, we are seeing clear evidence of the potential of gene therapy to effectively, over several years, halt motor neuron loss and alter the course of SMA Type 1 with a single dose.”
Among patients receiving the proposed therapeutic dose (Cohort 2), 11/12 patients (91.7 percent) were able to hold their head erect for >= three seconds and sit without support for >= five seconds, 10 patients (83.3 percent) were able to sit without support for >= 10 seconds, 9 patients (75.0 percent) were able to sit without support for >= 30 seconds, and two patients each (16.7 percent) were able to stand alone, walk with assistance and walk alone.
As of March 8, 2019, all patients maintained the motor function and milestones gained during the trial following treatment with Zolgensma. In addition, no patients had any additional requirements for ventilatory or nutritional support.
Two of the four patients who required Bilevel Positive Airway Pressure (BiPAP) support at the beginning of the long-term follow-up study no longer required it regularly. No new treatment-related adverse events have emerged during the follow-up period.
Patients in START were treated with gene therapy alone during the 24-month study duration. In the long-term follow-up study, 7 of 10 (70 percent) patients remain on monotherapy alone. Initiation of combination therapy was at parental and physician discretion and was not due to loss of motor function.
The sustained clinical impact following dosing suggests that Zolgensma effectively halts motor neuron loss and adds to the evidence of the long-term durability of Zolgensma.
This report was written using materials from Novartis’ press release and edited for readability. For more information, please see the press release here.