On May 24, the US Food and Drug Administration (FDA) approved Zolgensma (onasemnogene abeparvovec-xioi), the first gene therapy approved to treat children less than 2 years of age with spinal muscular atrophy (SMA), the most severe form of SMA and a leading genetic cause of infant mortality.

“Today’s approval marks another milestone in the transformational power of gene and cell therapies to treat a wide range of diseases,” said acting FDA commissioner Ned Sharpless, MD, “With each new approval, we see this exciting area of science continue to move beyond the concept phase into reality. The potential for gene therapy products to change the lives of those patients who may have faced a terminal condition, or worse, death, provides hope for the future. The FDA will continue to support the progress in this field by helping to expedite the development of products for unmet medical needs through the use of review pathways designed to advance innovative, safe, and effective treatment options.”

SMA is a rare genetic disease caused by a mutation in the survival motor neuron 1 (SMN1) gene. The gene encodes the survival motor neuron (SMN) protein—a protein found throughout the body, which is critical for the maintenance and function of specialized nerve cells, called motor neurons. Motor neurons in the brain and spinal cord control muscle movement throughout the body. If there is not enough functional SMN protein, then the motor neurons die, leading to debilitating and often fatal muscle weakness. SMA caused by mutations in the SMN1 gene is generally classified into several subtypes, based on the age of onset and severity; infantile-onset SMA is the most severe and most common subtype. Children with this condition have problems holding their head up, swallowing, and breathing. These symptoms may be present at birth or may present by the age of 6 months.

“Children with SMA experience difficulty performing essential functions of life. Most children with this disease do not survive past early childhood due to respiratory failure” said Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research. “Patients with SMA now have another treatment option to minimize the progression of SMA and improve survival. This approval demonstrates the continued momentum of this promising new area of medicine and the FDA’s commitment to supporting and helping expedite the development of these products.”

Zolgensma is indicated for the treatment of children less than 2 years of age with SMA. The product is an adeno-associated virus vector-based gene therapy that targets the cause of SMA. The vector delivers a fully functional copy of human SMN gene into the target motor neuron cells. A one-time intravenous administration of Zolgensma results in expression of the SMN protein in a child’s motor neurons, which improves muscle movement and function, and survival of a child with SMA. Dosing is determined based on the patient's weight.

The safety and effectiveness of Zolgensma is based on an ongoing clinical trial and a completed clinical trial involving a total of 36 pediatric patients with infantile-onset SMA between the ages of approximately 2 weeks and 8 months at study entry. The primary evidence of effectiveness is based on results from the 21 patients treated with Zolgensma in the ongoing clinical trial. In this trial, there are 19 remaining patients, who range in age from 9.4 to 18.5 months; 13 of these 19 patients are at least 14 months of age. Compared to the natural history of patients with infantile-onset SMA, patients treated with Zolgensma also demonstrated significant improvement in their ability to reach developmental motor milestones (eg, head control and the ability to sit without support).

The most common side effects of Zolgensma are elevated liver enzymes and vomiting. Zolgensma has a boxed warning that acute serious liver injury can occur. Patients with pre existing liver impairment may be at higher risk of experiencing serious liver injury. Clinical examination and laboratory tests to assess liver function should be completed prior to treatment with Zolgensma, and patients’ liver function should be monitored for at least 3 months after Zolgensma administration.

Certain vaccines are contraindicated for patients on a substantially immunosuppressive steroid dose. Therefore, caregivers should consult with their health-care professional to determine if adjustments to the patient’s vaccination schedule are necessary to accommodate concomitant corticosteroid administration.

The FDA granted this application Fast Track, Breakthrough Therapy, and Priority Review designations. Zolgensma also received Orphan Drug designation, which provides incentives to encourage the development of drugs for rare diseases.

The FDA also awarded the manufacturer a rare pediatric disease priority review voucher, under a program intended to encourage the development of new drugs and biological products for the prevention and treatment of certain rare pediatric diseases.

The FDA granted the approval of Zolgensma to AveXis Inc.

The FDA, an agency within the US Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.