Short-term clinical outcomes of onasemnogene abeparvovec treatment for spinal muscular atrophy.

Introduction: Spinal muscular atrophy (SMA) is a degenerative neuromuscular disorder long recognized as the most common genetic cause of infantile mortality described so far. However, the emergence of some innovative therapies, such as nusinersen and onasemnogene abeparvovec (AVXS-101), have made it possible to change the disease course of SMA.

Methods: In this study, five SMA type 1 and one SMA type 2 patients who received AVXS-101 were enrolled (7-24 months of age when administered). They were all previously treated with nusinersen, 4-5 times including loading doses, but stopped nusinersen maintenance after injection of AVXS-101. Patients were regularly followed up with laboratory tests and functional assessments after administration.

Results: Liver enzymes (aspartate aminotransferase, alanine aminotransferase, and gamma-glutamyl transferase) and monocyte count tended to be elevated but normalized after several weeks. Platelets and white blood cells were transiently decreased for a few weeks after injection. Prolonged elevation of liver enzymes was associated with steroid tapering earlier than 1 month post treatment. During the follow-up period (ranging from 5 to 17 months after injection), all patients showed improved motor function and there was no case of mortality or requirement for permanent ventilatory support. For one patient, use of bilevel positive airway pressure could be reduced from 16 h to 8 h a day during sleep at 6 months post treatment.

Conclusion: Our experience of AVXS-101 treatment has shown that a single intravenous dose could be safe and effective for SMA patients without the need for any maintenance treatment.