OBJECTIVES: Spinal muscular atrophy (SMA) is a neurodegenerative disease caused by SMN1 gene deletion/mutation. Disease severity (SMA type) correlates with SMN2 gene copy number. Gene therapy (onasemnogene abeparvovec-xioi) provides sustained, continuous production of SMN protein, and is FDA-approved, with ongoing trials for SMA types 2/3, and presymptomatic treatment for all SMA types. With effective treatments available, many US states are implementing newborn screening (NBS) to detect SMN1 deletions and SMN2 copies, providing early diagnosis and the option of presymptomatic treatment. It is important to understand the economic impact of NBS and presymptomatic gene therapy.

METHODS: A decision-analytic model was built to assess the cost effectiveness of NBS in 10,000 hypothetical newborns from a US third-party payer perspective. In the base case, NBS with presymptomatic gene therapy for any positive SMA test was compared to no NBS with gene therapy for symptomatic SMA type 1. Inputs and assumptions on lifetime costs and utilities for SMA types were obtained from the 2018 Institute for Clinical and Economic Review SMA report; other values were sourced from published literature. Model outputs included costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs). Scenario and sensitivity analyses tested model robustness.

RESULTS: In the base case, NBS for 10,000 newborns with presymptomatic gene therapy for any positive test and treatment cost $3,150,087 and produced 269,996 QALYs. The ICER was $15,181/QALY compared to no NBS with gene therapy for symptomatic SMA type 1. In the scenario analysis, if only presymptomatic patients with ≤3 SMN2 copies are treated, NBS was dominant.

CONCLUSIONS: Compared to no screening, NBS with presymptomatic gene therapy for SMA is a cost-effective option from the US payer perspective. Results were most sensitive to treatment strategies (i.e. treatment depending on SMN2 copy number) and the distribution of SMA types; screening costs had a minimal impact.