2024 update: European consensus statement on gene therapy for spinal muscular atrophy

Area of Science:

• Neurology
• Genetics
• Pediatrics

Background:

• Spinal muscular atrophy (SMA) is a common genetic disorder, historically a major cause of infant mortality.
• Recent advancements include disease-modifying treatments, particularly gene therapy, significantly improving outcomes for SMA type 1, especially when initiated presymptomatically.
• Onasemnogene abeparvovec (Zolgensma®), an AAV9-based gene therapy, is approved for SMA patients with up to three SMN2 gene copies or SMA type 1 presentation.

Purpose of the Study:

• To establish consensus among European experts on the rational use of onasemnogene abeparvovec in SMA treatment.
• To evaluate emerging evidence regarding the efficacy and safety of onasemnogene abeparvovec in older and heavier SMA patients.
• To provide updated guidance reflecting the evolving role of gene therapy in managing spinal muscular atrophy.

Main Methods:

• A European neuromuscular expert working group was convened using a modified Delphi methodology.
• Experts assessed recent clinical trial data and real-world evidence on onasemnogene abeparvovec.
• The group developed consensus statements based on the evaluated evidence over a three-year period.

Main Results:

• Twelve consensus statements were formulated regarding the use of onasemnogene abeparvovec.
• Strong consensus was achieved on 9 statements, with consensus on the remaining 3.
• The findings reflect the expanding application and evidence base for gene therapy in SMA.

Conclusions:

• The consensus statements provide guidance for the appropriate selection of SMA patients for onasemnogene abeparvovec treatment.
• The evolving evidence supports the use of gene therapy in a broader range of SMA patients.
• These expert-driven recommendations aim to optimize the risk-benefit profile of onasemnogene abeparvovec therapy.