Zolgensma

Zolgensma (onasemnogene abeparvovec-xioi) is a one-time gene therapy treatment for spinal muscular atrophy (SMA). It was approved by the U.S. Food and Drug Administration in 2019 for children with SMA under 2 years of age and is given through an intravenous (IV) infusion. Boston Children’s is a designated Center of Excellence for administering this treatment.

Zolgensma replaces the SMN1 gene, which is missing or broken in children with SMA, with a healthy copy of that gene. The new, healthy SMN1 gene restores production of the SMN protein. This protein helps motor neuron cells in the spinal cord and brainstem work correctly and improves muscle and nerve function.

To deliver the SMN1 gene, we use a “vector” made from a harmless virus called AAV9 that is good at getting inside of cells.

Children under 2 years old with a genetic test confirming that they have SMA (showing a mutation in both copies of the SMN1 gene) may be eligible for Zolgensma. This includes children who have received nusinersen (Spinraza) or risdiplam (Evrysdi) in the past.

Zolgensma is not a complete cure for SMA, but studies have indicated that it improves motor function and reduces the need for breathing support, especially when given early in infancy. It was evaluated in two main clinical trials. 

One trial, called STR1VE, treated 22 infants with SMA Type 1 with Zolgensma before six months of age. At 14 months of age, 20 of the 22 were able to breathe without ventilation support. At 18 months, 21 of the 22 showed substantial improvements in motor function: 19 were able to feed orally, 13 could sit unaided for 30 seconds at least once, 17 had head control, and 13 were able to roll from side to side. One child, treated at 1 month of age, was able to stand and walk independently.

An earlier trial, called START, enrolled 15 infants with SMA Type 1 under 8 months of age. The first three infants received low doses of Zolgensma. Once this was found to be safe, the remaining 12 infants received a higher dose. Similar to the STR1VE trial, none of these 12 children needed breathing support, and 11 showed substantial improvements in motor function.

START is also running a long-term follow-up study. As of May 2022, all 10 children who continued in the study (now 6.6 to 7.9 years old) have maintained the motor milestones they achieved earlier, seven of 10 do not need breathing support, and three of 10 can now stand with assistance.

Zolgensma is given through a single intravenous (IV) infusion in Boston Children’s Hospital’s Infusion and Day Treatment Program — Boston. Treatment does not typically require an inpatient hospital stay.

The infusion takes about 60 minutes. We will keep your child in the infusion clinic for at least three hours afterward, watching for any side effects.

After that, your family must stay close enough to the hospital to be able to return for follow-up visits a few times per week for up to three months including laboratory studies, electrocardiograms (EKGs), and echocardiograms. Meanwhile, a clinician in our Spinal Muscular Atrophy Program will evaluate your child’s motor skills to see how well the treatment is working.

Your child will be started on a corticosteroid medication such as prednisone the day before infusion and continue for at least 90 days afterward. This medication helps to lower the risk of liver inflammation, which can sometimes occur after Zolgensma treatment.

Zolgensma treatment is safe provided your child is monitored with lab tests for at least three months to watch for and treat potential side effects. The most common of these — affecting 5 percent or more of children — are vomiting and elevated liver enzymes.

Though uncommon, liver inflammation is the most serious potential side effect. To prevent any liver damage, we give corticosteroids (prednisone) just before Zolgensma gene therapy and for the three months after, and we will monitor your child closely by measuring liver enzymes in their blood.

We also watch for high levels of troponin-I (a cardiac enzyme), which may indicate short-term damage to heart muscle, and monitor platelet counts, which can sometimes be reduced temporarily after treatment, causing a risk of bleeding. Finally, we monitor for a rare complication known as thrombotic microangiopathy, in which blood clots form in the small blood vessels. 

The corticosteroids we give to prevent liver inflammation can suppress the immune system, making children more susceptible to infections. We encourage precautions to prevent infections and may recommend holding off on any vaccinations while your child is on corticosteroid treatment — or having those vaccinations done before treatment.

Because Zolgensma is so new, it is not yet clear to what extent health insurance providers will cover it. We encourage you to talk with your health insurance company and care team. Boston Children’s Financial Services staff can guide you through the insurance approval process. In addition, Zolgensma’s manufacturer, Novartis, offers the OneGene Program, which can provide some types of financial assistance to eligible families.

Contact the Spinal Muscular Atrophy Program.

• Phone: 617-919-6814
• Email: SMAProgram@childrens.harvard.edu