Novartis Announces Positive Phase 3 Results for Zolgensma in Type 1 Spinal Muscular Atrophy, Awaiting FDA Decision in May

Recently,NovartisNovartis’ subsidiary AveXis announced that Zolgensma, a gene therapy for the treatment of type 1 spinal muscular atrophy (SMA), in the Phase 3 trial named STR1VEClinical Trialwith positive interim results. Zolgensma can prolong event-free survival in infants, improve motor function scores, and enable them to achieve developmental milestones that would be unattainable without treatment. If approved, this therapy will becomeFDAThe second approved in vivo gene therapy.

SMA is a severe neuromuscular disease in which patients experience progressive muscle weakness and paralysis due to the death of motor neurons. SMA is caused by defects in the SMN1 gene, which encodes the survival motor neuron (SMN) protein. SMA is the leading cause of infant mortalityGeneticsone of the factors. In the most severe cases of type 1 SMA, due to rapid muscle atrophy, more than 90% of patients die or require permanent respiratory support within 24 months after birth.

Zolgensma is an AAV9 virus-basedCarriergene therapy that delivers a transgene expressing the SMN protein via the AAV9 virusCarrieradministered into the patient’s body. It has received Breakthrough Therapy Designation and Priority Review status from the FDA, and is expected to receive approval in May this year.FDAResponse.

In this open-label, single-arm, single-dose, multicenterClinical TrialAmong them, patients with Type 1 SMA aged less than 6 months received treatment with Zolgensma. The trial results showed that as of September 27, 2018, 21 out of the 22 treated patients were still alive and had not experienced any adverse events. Their median age was 9.5 months. According to the natural history of Type 1 SMA, approximately 50% of infants would die or require permanent respiratory support by 10.5 months of age.

The CHOP-INTEND score, which assesses patients’ motor function, increased by an average of 7 points one month after gene therapy and by an average of 11.8 points three months after treatment. This demonstrates an improvement in patients’ motor function compared to baseline, a metric that is closely associated with the ability to achieve expected developmental milestones.

A subset of patients receiving treatment achieved a series of motor milestones, including maintaining head alignment for more than 3 seconds, rolling over, and sitting up without assistance for more than 30 seconds. Over time, the proportion of patients reaching these milestones increased.

This trial represents the first analysis of the biodistribution of Zolgensma in humans. The study demonstrated that Zolgensma successfully transduced central nervous system tissues, including motor neurons in the brain and spinal cord. Furthermore, patients treated with Zolgensma exhibited a substantial number of motor neurons in their spinal cord tissues, which maintained normal size and morphology. In contrast, motor neurons were scarce in the tissues of untreated patients with type 1 spinal muscular atrophy (SMA). These data support the mechanism of action observed for Zolgensma in preclinical mouse and non-human primate models.

“The data from the STR1VE trial further support the results we observed in our prior pivotal Phase 1 START trial, including that Zolgensma can prolong survival and help achieve motor milestones,” said Dr. Olga Santiago, Chief Medical Officer at AveXis. “These data add to the body of evidence supporting Zolgensma for the treatment of Type 1 SMA.”BioonBioon.com）