To assess the cost-effectiveness of both single-dose gene-replacement therapy with AVXS-101 (onasemnogene abeparvovec) and current standard of care (nusinersen) in patients with Spinal Muscular Atrophy Type 1 (SMA1) in Japan.

We adapted a multi-state Markov model originally developed for the United States. Health state transitions were based on milestone attainment (sitting, walking) from published clinical trials. Survival benefit was estimated using long-term data from both sitting and walking SMA patients and from natural history. Costs related to drug acquisition and administration, adverse events, and SMA care were sourced from published medical service fees and literature, reimbursement guidelines, and Japan claims database research with support from medical expert interviews. AVXS-101 drug price (¥232M per dose) was referred from the US. Utilities were from values used by the US Institute for Clinical and Economic Review, incorporating values used in the UK NICE evaluation of nusinersen, and general population utility scores for Japan. Expected costs and QALYs were calculated for lifetime.

Discounted at 2%, per-patient total quality-adjusted life-years (QALYs) were 14.5 for AVXS-101 and 2.5 for nusinersen (if undiscounted: 23.3 and 3.3, respectively). Estimated discounted lifetime costs for nusinersen were ¥330M. Lifetime discounted costs for AVXS-101 were ¥266M per patient, resulting in cost savings and QALY gains compared to nusinersen – AVXS-101 dominant. In a pessimistic scenario where durability of AVXS-101 is limited to 25 years, AVXS-101 would deliver 10.4 QALYs per patient at a cost of ¥265M and would thus still be dominant over nusinersen. In a scenario where AVXS-101 benefits are based on patients treated before age 6 months only, AVXS-101 delivers 16.1 QALYs at a cost of ¥264M – AVXS-101 dominant.

AVXS-101 is cost-effective and likely to be dominant compared to nusinersen in Japan.