OBJECTIVES:

Spinal muscular atrophy (SMA) is a rare neuromuscular disease caused by survival motor neuron (SMN) 1 gene mutation. Onasemnogene abeparvovec (ONA) is a single-administration gene therapy intended to be curative. We estimated the cost-effectiveness of ONA compared to best supportive care (BSC) in pre-symptomatic newborns diagnosed with SMA and two SMN2 copies—the most severe manifestation.

METHODS:

A health state transition model was developed from the US healthcare sector perspective. The states included 'not sitting,' 'sitting,' 'standing,' 'walking,' 'permanent ventilation (PV),' and 'death.' We directly extracted the proportions of children in each state from the single-arm SPR1NT trial, which reported that no patient needed 'PV' for 18 months after infusing ONA. After that, patients remained in their states until death. With BSC, motor functions did not improve from 'not sitting,' and patients transitioned only to 'PV' or 'death’ based on the sham-controlled ENDEAR trial for nusinersen. We applied state-specific mortality estimates from several sources, including natural history data and U.S. life tables. Health state utilities were from studies on nusinersen, except for the walking state, which used age-specific estimates from the U.S. general population. The model included a list price of $2.125 million for ONA and monthly health costs estimated from published commercial healthcare claims. Model outcomes included total QALYs, total costs, and the incremental cost-effectiveness ratio (ICER). Costs (2021 dollars) and outcomes were discounted at 3%. We explored uncertainties through one-way and scenario analysis that tested regression to 'not sitting' in 30% of patients from the 'sitting.'

RESULTS:

ONA yielded incremental quality-adjusted life years gained of 21.76 at an additional cost of $2,124,154, with an ICER of $96,977. The ICER was most sensitive to time horizon and ONA cost. The scenario analysis increased the ICER to $101,192.

CONCLUSIONS:

Treatment with ONA for pre-symptomatic SMA was cost-effective at an ICER threshold of $100,000.