Virtual Conference
Eugeniya Uvakina

Eugeniya Uvakina

National Medical Research Center of Children's Health, Russia

Title: Safety profile of onasemnogene abeparvovec in children with spinal muscular atrophy at national medical research centre of children`s health Russia


Goal. To evaluate the safety profile of onasemnogene abeparvovec (Zolgensma®) gene replacement therapy in children with spinal muscular atrophy (SMA) in real clinical practice.

Materials and methods. The study included 30 SMA children who received gene replacement therapy with onasemnogene abeparvovec (Zolgensma®) at the National Medical Research Centre of Children`s Health, Russia. 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 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 parameters 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 prednisolone dose up to 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 parameteres, the clinical condition of the children remained stable. The average duration of prednisolone intake was 17.8 ± 6.6 weeks.