First Comprehensive Review of SMA Drugs Offers Long-Term Insights, Outcome Gaps

A new review study provides a detailed, long-term comparison at how patients with spinal muscular atrophy (SMA) fared on different therapies, and found that motor function improved across the board, with notable gaps in other health outcomes.

Researchers analyzed data from 21 studies involving 1,374 patients treated with Spinraza (nusinersen), Evrysdi (risdiplam), and Zolgensma (onasemnogene abeparvovec-xioi) for up to 48 months of follow-up. Unlike other studies that have reported clinical results for individual SMA medications, this review synthesizes data about all the approved treatments. Corresponding author Doris Giess, M.B.B.S., M.P.H., of the Austrian Institute for Health Technology and her co-authors said it was first such review of SMA medications.

Doris Giess, M.B.B.S.,M.P.H.

Giess and her co-authors found that all three therapies were effective in improving motor function for up to 48 months of follow-up. The degree of improvement varied based on when treatment was initiated and patients’ baseline function, with early intervention consistently leading to better outcomes.

Safety profiles of the therapies were generally favorable, with adverse events common, though they were rarely classified as treatment-related, with the exception of post-lumbar puncture syndrome in Spinraza studies.

The researchers found no significant improvements in respiratory and nutritional outcomes across the studies. In some cases, particularly for severe SMA, there was an increased need for respiratory and nutritional support over time.

“Given that respiratory issues are the primary non-neurological complication and leading mortality cause in SMA, this finding is critical,” Giess and her colleagues wrote.

The researchers also highlighted the fact that few studies they reviewed included quality of life endpoints in their assessments, leading to a lack of insight into how these therapies might impact patients in areas other than efficacy and safety.

The study concluded that the high cost of these therapies, coupled with an uncertainty in how long patients will continue to see motor improvements, present ongoing challenges for patients, physicians and payers in terms of coverage decisions and value assessment.

“The fact that currently the treatments appear at most to change the disease trajectory (particularly in SMA 1) from certain death to severe chronic illness with unknown long–term prognosis, initiates a difficult ethical discussion,” the study authors wrote.

The study, “An updated systematic review on spinal muscular atrophy patients treated with nusinersen, onasemnogene abeparvovec (at least 24 months), risdiplam (at least 12 months) or combination therapies,” was published in June in The European Journal of Paediatric Neurology.