Gene Therapy Approved for Children with Spinal Muscular Atrophy
May 24, 2019 – The U.S. FDA has approved Zolgensma® (onasemnogene abeparvovec-xioi), manufactured by AveXis, a Novartis company. It is the first and only gene therapy indicated to treat spinal muscular atrophy (SMA). The FDA has approved its use in children who are less than two years old and have SMA with bi-allelic mutations in the survival motor neuron 1 (SMN1) gene.
The leading genetic cause of infant mortality, SMA occurs when a mutation interferes with production of Survival Motor Neuron (SMN) protein. This in turn causes motor neurons to deteriorate and eventually die. The resultant muscle weakness and wasting leads to problems performing everyday functions of life, including sitting, swallowing, and even breathing. Although there are multiple types of SMA, Type 1, which manifests in infancy, is the most common and the most severe. Patients diagnosed with this type often die of respiratory failure in infancy or early childhood.
A one-time, single-dose treatment, Zolgensma addresses the root cause of SMA by delivering fully functional copies of the SMN gene to the body. Patients treated with Zolgensma in an ongoing clinical trial have shown improvements in survival and in achievement of developmental milestones, such as sitting without support, compared to the natural history of disease. Seventy-five percent of patients in the high-dose cohort of a completed clinical trial were able to sit without support for at least 30 seconds, while 16.7% were able to stand and walk unaided. However, the use of Zolgensma in patients with advanced SMA (complete paralysis, permanent ventilator dependence) has not been evaluated.
Recommended dosing for Zolgensma, which is administered via intravenous (IV) infusion, is based on the patient’s weight. Corticosteroids should be given both before and after the transfusion. According to a black box warning, serious liver injury can occur with Zolgensma. The patient’s liver function should be assessed prior to and at least three months after infusion.
AveXis has launched Zolgensma at a wholesale acquisition cost (WAC) of $2,125,000. According to the manufacturer, a plan is available to allow insurers to pay the full cost of the treatment over the course of five years.