Safety of Onasemnogene Abeparvovec Administration to Type 1 SMA Patients Who Have Received Risdiplam.

Abstract: Three therapies are now available for the treatment of type 1 spinal muscular atrophy: onasemnogene abeparvovec (OA), nusinersen, and risdiplam. We present a retrospective, single-center case series detailing our center's experience with six patients diagnosed with type 1 spinal muscular atrophy who switched from risdiplam to OA. Risdiplam was discontinued the day before the OA infusion, and we evaluate the safety aspects of this switch. All patients continued risdiplam until the day before administration of OA, with a wash out period of between 24 and 33 hours prior. All patients have had follow-up for at least 12 weeks, while 3 patients who lived locally received ongoing follow-up ranging from 14 to 27 months after OA infusion. All patients remained stable or improved in their motor scores and need for ventilatory support and feeding support requirement. Adverse events reported after OA switch included tachycardia, fever, nausea, vomiting, raised transaminases, and mild neutropenia. All adverse events in these children were either known adverse events of OA or were not considered secondary to OA or risdiplam treatment. No unexpected adverse event was demonstrated post-OA in patients stopping risdiplam a day before OA infusion. Data presented here suggest that stopping risdiplam a day before OA treatment did not seem to be associated with increased risk.