The US Food and Drug Administration (FDA) has accepted a Biologics License Application (BLA) as well as granted Priority Review for AVXS-101, now onasemnogene abeparvovec (Zolgensma), a therapy for spinal muscular atrophy Type 1.
Spinal muscular atrophy (SMA) Type 1 is a devastating progressive neuromuscular disease that affects infants with a defective or missing SMN1 gene. These infants lose motor neurons necessary for functions including breathing, swallowing, speaking, and walking. Untreated, SMA Type 1 leads to paralysis or death, generally by the child’s second birthday.
Novartis’ gene replacement therapy is a one-time infusion that replaces the defective or missing SMN1 gene with a functional copy that can create SMN protein and prevent the loss of motor neurons.
“This important step by the FDA brings us ever closer to delivering Zolgensma to patients with SMA Type 1. Babies affected by this rare disease are currently faced with debilitating disease progression and lifelong invasive chronic treatment. As a one-time infusion that addresses the genetic root cause of SMA without the need for repeat dosing, Zolgensma represents a potentially significant therapeutic advance for these patients and their families,” said David Lennon, PhD, president of AveXis, a Novartis company.
The onasemnogene abeparvovec BLA is supported by data from the START trial. The phase 1 trial included 15 patients infused with the therapy between .9 to 7.9 months of age. Cohort 1 (n = 3) received a low dose and Cohort 2 (n = 12) received a high dose. While 90% of patients with untreated SMA Type 1 die or require permanent ventilation by 24 months of age, at a 24-month follow up all 15 patients (100%) were event-free.
Among Cohort 2 participants at the 24-month follow up, 11 patients (91.7%) were able to hold their head erect for ≥3 seconds and sit without support for ≥5 seconds; 10 patients (83.3%) were able to sit unsupported for ≥10 seconds; 9 patients (75.0%) were able to sit unsupported for ≥30 seconds; and 2 patients (16.7%) were able to stand and walk alone.
The most common side effect of Zolgensma in the trial was elevated liver enzymes.