CADTH Recommends Gene Therapy for Infants With Rare Genetic Disorder

  • Onasemnogene abeparvovec (Zolgensma) is the first gene therapy used to treat spinal muscular atrophy — a rare progressive and life-threatening condition that often begins in childhood and is caused by a genetic mutation.
  • Conditions for reimbursement include a price reduction and clinical criteria for initiating treatment.

Today, CADTH recommends that Canada’s public drug plans (except Quebec) reimburse, with conditions, onasemnogene abeparvovec for infants with spinal muscular atrophy (SMA). SMA is a debilitating genetic condition that causes muscles throughout the body to weaken because cells in the spinal cord and brainstem do not work correctly. The reimbursement recommendation was made by the independent Canadian Drug Expert Committee at its March 2021 meeting.

The new treatment, under the brand name of Zolgensma and licensed by Novartis Pharmaceuticals Canada Inc., is the first-ever gene replacement therapy for SMA. It is indicated to treat pediatric patients with 5q SMA with biallelic mutations (those that occur in both alleles of a single gene) in the survival motor neuron 1 (SMN1) gene and 3 or fewer copies of the SMN2 gene; or infantile-onset SMA. It is a 1-time treatment that is delivered via intravenous infusion.

The recommendations for reimbursement include the following.


  • There is genetic documentation of 5q SMA with biallelic mutations in the SMN1 gene.
  • Patients are symptomatic or pre-symptomatic with 1 to 3 copies of the SMN2 gene.
  • Patients are aged 180 days (6-months-old) or younger.
  • Patients do not currently require permanent feeding or ventilatory support (either invasive or non-invasive).


  • Patients are under the care of a specialist with experience diagnosing and treating SMA.
  • Reimbursement is limited to 1 lifetime administration of the treatment.


  • A reduction in price.

Among the reasons for the recommendation, the committee noted evidence from a pivotal phase III study of infants who were symptomatic or pre-symptomatic with 1 or 2 copies of the SMN2 gene. The evidence showed clinically meaningful benefits related to achieving motor milestones at 18 months of age and breathing without permanent ventilation at 14 months of age compared to an historical control cohort. Infants in this study were younger than 180 days at the time of the treatment infusion.

The committee also noted evidence from an ongoing phase III study of pre-symptomatic infants younger than 6 weeks of age with either 2 or 3 copies of the SMN2 gene. Interim analysis results showed all patients survived without permanent ventilation at 14 months of age and potentially achieving age-appropriate motor milestones.

Onasemnogene abeparvovec is provided as a kit priced at CA$2,910,500 — which is the 1-time total cost of acquiring the drug. There is substantial uncertainty about the cost-effectiveness of treatment, due largely to uncertainty about its long-term efficacy and because the treatment’s effectiveness compared with nusinersen, the only other available drug for SMA, could not be determined.

In arriving at the recommendation, the committee considered clinical evidence, economic evidence, information from the sponsor, input from 4 specialists experienced in treating SMA, and input from Cure SMA Canada and Muscular Dystrophy Canada on outcomes and issues important to patients and caregivers. The committee also acknowledged that despite the availability of 1 other drug for SMA, there is a significant need for new treatments.

Brent Fraser, Vice-President of Pharmaceutical Reviews at CADTH, said:

“A diagnosis of SMA has a devastating impact on children and caregivers. The arrival of a new treatment that can help infants potentially achieve motor milestones and delay the need for ventilation is a huge advancement. Despite the extraordinary cost of treatment, CADTH recommends reimbursing this therapy for infants up to 6 months of age because the evidence that is available to us right now shows the benefit is greatest for these young patients, especially when treatment is started as early as possible.”

Implementation Considerations

As part of CADTH’s fit-for-purpose reimbursement review process, special attention is given to the implementation issues that may arise with the introduction of novel cell or gene therapies. In its recommendation, the expert committee discussed the availability of genetic testing, sequencing matters relative to nusinersen, and considerations for product listing agreements.

Other Recommendations for SMA Treatments

In 2020, CADTH recommended reimbursing nusinersen, with conditions, for the treatment of 5q SMA. Risdiplam, a daily oral therapy for SMA, is currently under review and will be considered by the Canadian Drug Expert Committee in April 2021.

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