OBJECTIVES: Spinal Muscular Atrophy Type 1 (SMA1) is a rapidly progressing, debilitating neurodegenerative disease resulting from bi-allelic survival motor neuron 1 (SMN1) deletion/mutation. Onasemnogene abeparvovec (AVXS-101), an investigational gene replacement therapy, delivers human SMN via one-time administration. This study highlights the value of AVXS-101 for SMA1 and assesses its cost-effectiveness versus the current standard of care, nusinersen, in the U.S.

METHODS: Twelve SMA1 patients were treated with a one-time intravenous AVXS-101 infusion (NCT02122952; cohort 2; proposed therapeutic dose); event-free survival (composite endpoint of time-to-death or permanent ventilation), pulmonary/nutritional interventions, swallowing, hospitalizations, CHOP-INTEND scores, and safety were assessed for 2 years. A multi-state survival Markov model over a lifetime was developed. Motor milestones, survival, healthcare costs, and quality-adjusted life-years (QALYs) were estimated using natural history and clinical trial data for SMA1 patients. Quality of life utility weights were obtained from the CHERISH trial.

RESULTS: All 12 patients survived event-free; 7 did not require daily noninvasive ventilation; 11 had stable/improved swallowing; and 11 were able to speak. Patients experienced a mean 2.1 (range, 0–7.6) hospitalizations/year and 1.4 (0–4.8) respiratory hospitalizations/year. CHOP-INTEND rapidly increased by 9.8 (standard deviation [SD], 3.9) and 15.4 (SD, 6.4) points at 1- and 3-months post-dose, respectively. At long-term follow-up, 11 patients sat unassisted, 4 stood with assistance, and 2 walked independently. Adverse events included elevated serum aminotransferase levels, attenuated by prednisolone. Undiscounted total QALYs/patient were 30.3 for AVXS-101 and 7.2 for nusinersen. Estimated discounted lifetime costs were $6.33M for nusinersen and $3.7-4.7M for AVXS-101 at hypothetical prices of $2-3M/dose, resulting in cost savings and QALY gains compared to nusinersen.

CONCLUSIONS: In the NCT02122952 study, AVXS-101 improved survival and motor function in SMA1 patients while being cost-effective compared to nusinersen. The reduced healthcare utilization in treated infants could also alleviate patient/caregiver/societal burden and improve quality of life.