As of September 2018, 95% of children treated with Zolgensma were alive and did not require permanent ventilation.
Olga Santiago, MD
Interim results from the phase 3 STR1VE clinical trial of Zolgensma have indicated positive efficacy outcomes for children with spinal muscular atrophy (SMA) Type 1. The results showed 95% event-free survival without the need for permanent ventilation to an average age of 9.5 months and increases in motor function scores 1 and 3 months after treatment.
Zolgensma (onasemnogene abeparvovec; AVXS-101) is a gene therapy that is administered in a one-time intravenous infusion. The therapy addresses the root cause of SMA by delivering a functioning SMN1 gene to motor neurons without a copy.
The interim study results were presented on April 15, 2019 at the 2019 Muscular Dystrophy Association (MDA) Clinical and Scientific Conference in Orlando, Florida.
"These STR1VE data reinforce what was seen in the pivotal phase 1 START trial, including trends toward prolonged survival and milestone achievement never seen in the natural history of the untreated disease," said Olga Santiago, MD, Chief Medical Officer, AveXis. "With a patient population and baseline characteristics closely matched to the START trial, these data build upon the body of evidence supporting the use of Zolgensma for SMA Type 1."
The open-label, ongoing, single-arm STR1VE trial is evaluating the efficacy and safety of a single intravenous infusion of Zolgensma in infants under 6 months of age with spinal muscular atrophy type 1. The trial enrolled 22 patients.
As of September 27, 2018, 95% of participants (21/22) were alive and event-free at a median age of 9.5 months. Untreated, 50% of children with SMA Type 1 will not survive to reach 10.5 months of age or will require permanent ventilation by that age. Patient eligibility criteria in STR1VE were comparable that in the phase 1 START trial.
Motor function was gauged by Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND) scores. Average CHOP-INTEND scores increased by 7.0 points a month after treatment and by 11.8 points 3 months after treatment.
As of September 27, 2018, there were 3 participants (13.6%) able to sit up unassisted for at least 30 seconds. By December 31, 2018, there were 8 participants (36.4%) who had achieved that milestone.
By the end of 2018, 1 patient (4.5%) could even stand with assistance, defined as the child holding their own weight for ≥2 seconds.
Safety results were comparable to those of the START trial. Adverse events including elevated transaminases, platelet count decrease, and thrombocytopenia were observed, but deemed transient. One trial participant passed away due to respiratory failure, which the investigators and independent Data Safety Monitoring Board determined to be unrelated to treatment. The patient had experienced significant progress, with a 27-point increase in CHOP-INTEND score from baseline to 5 months.
The STR1VE trial is expected to conclude in 2020.
In December 2018, AveXis submitted a Biologics License Application (BLA) for Zolgensma for the treatment of spinal muscular atrophy Type 1, which the US Food and Drug Administration (FDA) accepted. Additionally, the treatment has been granted Breakthrough Therapy and Fast Track Designations, as well as Priority Review. The time of BLA submission, the company anticipated regulatory action in May 2019.