Safety profile of onasemnogene abeparvovec in children with spinal muscular atrophy

Abstract

Goal. To evaluate the safety profile of onasemnogene abeparvovec (Zolgensma®) gene therapy in children with spinal muscular atrophy (SMA) in real clinical practice. Materials and methods. The study included 30 SMA children who underwent gene replacement therapy with onasemnogene abeparvovec (Zolgensma®) from December 2020 to December 2021 at the Center for Pediatric Psychoneurology. All children had a diagnosis of SMA confirmed by molecular genetic methods, with no more than 3 copies of the SMN2 gene and the absence of antibodies to the adeno-associated virus serotype 9. The safety profile was assessed by monitoring the clinical and laboratory data of the patients after administration of onasemnogene abeparvovec. Clinical events included all changes in the child’s condition that could be associated with the administration of the drug (hyperthermia, decreased appetite, nausea, vomiting, stool disorders). Laboratory assessment included monitoring of complete blood count, biochemical blood tests, blood coagulation indices. The degree of laboratory changes was estimated according to common terminology criteria for adverse events (CTCAE version 5.0). Results. The safety profile of the drug Zolgensma® was studied in 30 children aged from 3 to 39 months, with a weight of 5.2 kg to 14.2 kg. Twenty-eight (93.3%) children had at least one clinical event associated with the administration of the drug. Hyperthermia was observed in 24 (80%) children, nausea and vomiting in 18 (60%) children, decreased appetite in 20 (66.7%) children, stool changes in 4 (13.3%) children. Monitoring of laboratory indices revealed thrombocytopenia and monocytosis in twenty-two (73.3%) children and neutropenia in twelve (40%) children in the general blood test. An increase in the level of transaminases was noted in all children, the CTCAE grade 1 was detected in fifteen (50%) children, the CTCAE grade 2 in 7 (23.3%) children, CTCAE grade 3 in 6 (20%) children, CTCAE grade 4 in 2 (6.7%) children. Children with CTCAE grade 3 required correction of the prednisone dose up 2 mg/kg per day for 2-4 weeks. Two children with CTCAE grade 4 required pulse therapy with methylprednisolone at a dose of 30 mg/kg per day. Regardless of the level of transaminases, no change in the level of total and direct bilirubin was observed in any case. A decrease in prothrombin time was observed in 14 (46.6%) children. An increase in the level of troponin I was detected in four (13.3%) children. In all cases of serious adverse events, according to laboratory indices, the clinical condition of the children remained stable. The average duration of prednisone intake was 17.8 ± 6.6 weeks. Conclusion. The safety profile of the drug onasemnogene abeparvovec (Zolgensma®) in real clinical practice in children with SMA is presented.