Fatal outcomes following onasemnogene abeparvovec in advanced-stage spinal muscular atrophy

Area of Science:

• Neurology
• Genetics
• Pediatrics

Background:

• Onasemnogene abeparvovec (OA) is approved for spinal muscular atrophy (SMA).
• Efficacy of OA in advanced SMA patients, particularly Type 1, requires further investigation.
• Thailand has historical survival data for SMA Type 1 patients.

Purpose of the Study:

• To assess the clinical effectiveness and adverse events of OA in advanced SMA patients in Thailand.
• To compare outcomes of OA therapy in advanced SMA patients with historical survival data for SMA Type 1.
• To evaluate OA's impact on motor function and survival in severe SMA cases.

Main Methods:

• An observational cohort study was conducted at Siriraj Hospital, Thailand, from May 2019 to April 2022.
• Eight SMA patients received OA therapy: five SMA Type 1 and three SMA Type 2.
• Patients were assessed for motor scores, need for ventilation/feeding support, and adverse events. Outcomes were compared to historical survival data.

Main Results:

• SMA Type 1 patients (n=5) required invasive ventilation and feeding support pre-treatment. Post-treatment, three showed motor score improvement, but none achieved new motor milestones. All SMA Type 1 patients experienced fatalities, with no survival improvement.
• SMA Type 2 patients (n=3) demonstrated motor score improvement without serious adverse events.
• OA did not significantly improve clinical outcomes or survival rates in advanced SMA Type 1.

Conclusions:

• Onasemnogene abeparvovec (OA) demonstrated limited efficacy in improving clinical outcomes and survival rates for advanced SMA Type 1 patients.
• Caution is advised when administering OA to severe SMA Type 1 cases.
• Further research is needed to establish specific guidelines for selecting patient subgroups for OA treatment.