Zolgensma (onasemnogene abearvovec-xioi) an investigational gene therapy for spinal muscular atrophy (SMA) is currently awaiting approval from the US Food and Drug Administration (FDA) to be the first-ever one-time gene therapy for SMA.
A spokesperson for Novartis told us the therapy addresses the monogenic root cause of SMA to prevent further muscle degeneration by providing a copy of the human SMN gene to halt disease progression. The therapy is delivered through an adeno-associated virus vector known as AAV9.
The spokesperson continued that the information on the infant’s death has been shared with regulators and the company does not anticipate any impact on the trajectory of Zolgensma’s FDA approval. It was reported that the infant died of a severe respiratory infection and neurological complications but autopsy results are still pending. The Phase III trial is still enrolling patients.
SMA is a rare genetic disease that leads to progressive muscle weakness, paralysis, and when Type I is left untreated death. In fact, 50% of infants with untreated SMA will die or require ventilation by 10.5 months of age.
During the trial, which resulted in one infant death, 21 out of the 22 patients aged 9.5 months were free from serious complications. Other patients demonstrated rapid improvement in motor function and achievement of motor milestones, including sitting without assistance, and standing without assistance – which are ‘unprecedented’ in the natural history of the disease.
Beyond the impact in SMA, a potential approval of the gene therapy will necessitate pricing discussions with payers specifically on the issue of one-time therapies, the spokesperson confirmed.,
“The introduction of one-gene therapies requires re-envisioning how we define the value of treatments, as well as how our health care system manages diagnosis, treatment, care and associated costs for patients with rare diseases,” the spokesperson said.
The spokesperson added, “Chronic treatments are costing the health care system tens of millions of dollars over a patient’s lifetime, and we are looking to change this paradigm with the introduction of one-time gene therapies.”
Should Zolgensma be approved it will challenge Biogen’s Spinraza, a once-a-trimester treatment which brought in $1.7bn (€1.52bn) in worldwide sales in 2018. Currently, Novartis looks to set the one-time treatment at $1.5m to $5m, according to a statement from the CEO.