A comprehensive, real-world study evaluating the efficacy and safety of onasemnogene abeparvovec (OA) in patients with spinal muscular atrophy (SMA) across Germany, Austria, and Switzerland (D-A-CH) underscores the critical impact of early intervention. The observational study, encompassing 343 individuals with SMA, reveals that functional motor improvement is significantly correlated with younger age at the time of gene therapy, with the most favorable outcomes observed in those treated before six weeks of age. These findings emphasize the importance of newborn screening programs and prompt treatment initiation to optimize patient outcomes.
The study, which leveraged data from the SMArtCARE registry and Swiss-Reg-NMD, included a diverse cohort of SMA patients, with ages ranging from 0 to 90 months at the time of OA administration (mean 14.0 months). Notably, 23% of patients were clinically presymptomatic at treatment. Half of the patients had previously received SMN2 splice-modifying drugs such as risdiplam or nusinersen before undergoing gene therapy.
Impact of Age on Treatment Outcomes
The analysis revealed a clear correlation between age at gene therapy and motor outcomes. Patients treated at a younger age, particularly those under six weeks old, carrying three SMN2 copies, and being clinically presymptomatic, exhibited the most significant functional motor improvements. Conversely, the likelihood of requiring ventilation or nutritional support increased significantly with older age at the time of GAT and remained stable thereafter. Pre-treatment with SMN2 splice-modifying drugs did not appear to significantly affect disease trajectories.
Safety Profile
The study also provided valuable insights into the safety profile of OA across different age groups. Liver-related adverse events occurred significantly less frequently in patients up to 8 months of age, while other adverse events were evenly distributed across all age and weight groups.
Clinical Implications
"Overall, motor, respiratory, and nutritional outcome were dependent on timing of GAT and initial symptom status. It was best in presymptomatic children treated within the first six weeks of life, but functional motor scores also increased significantly after treatment in all age groups up to 24 months," the researchers noted. The findings strongly advocate for SMA newborn screening and immediate treatment to achieve the best possible benefit-risk ratio.
This real-world evidence reinforces the importance of early diagnosis and intervention in SMA, highlighting the potential of onasemnogene abeparvovec to significantly improve outcomes when administered at a young age. The study provides clinicians and families with valuable data to inform treatment decisions and set realistic therapeutic goals.
