Experience of using onasemnogen abeparvovek in children with spinal muscular atrophy 5q with 2 or 3 copies of the SMN2 gene in a multidisciplinary center in Saint Petersburg

Aim. Evaluation of the efficacy and safety of onasemnogen abeparvovec (OA) therapy in patients aged 1–34 months with spinal muscular atrophy (SMA) 5q with 2 or 3 copies of the SMN2 gene at preclinical and manifest stages of the disease development in the conditions of Children’s City Multidisciplinary Clinical Specialized Center for High Medical Technologies in Saint Petersburg.

Materials and methods. According to the legislative acts of the Russian Federation and by decision of the Federal Council, children diagnosed with SMA without previous pathogenetic therapy received gene replacement therapy with OA in the conditions of the municipal children’s multidisciplinary clinical hospital in Saint Petersburg. Clinical efficacy was assessed initially and then every 6 months, lasting 24 months, using the motor assessment scales HINE-2 (qualitative neurological scale of infants), CHOP INTEND (for children unable to sit independently), and HFMSE (for patients capable of independent sitting). At the same time, the safety of OA was monitored by changes in clinical, laboratory and instrumental parameters.

Results. 19 children aged 1–34 months with a body weight of less than 21 kg received OA therapy in the period from June 2022 to January 2025. The average dynamics on motor scales every 6 months in children with preclinical and manifest SMA was: CHOP INTEND – +16.1 points, HFMSE – +13.5 points; qualitative changes in neurological status were fixed on the HINE-2 scale. Adverse events (weakness/drowsiness, pyrexia, nausea, vomiting) developed 3–5 days after administration of the drug and were transient in nature. Immune-mediated liver hyperfermentemia of varying severity was detected in all patients: most often with an increase in alanine aminotransferase and aspartate aminotransferase values less than 2 times the norm – 15 (78.9 %) children in the range of 3–4 weeks; 2 (10.5 %) children had a second wave of hyperfermentemia at week 7–8. Severe hyperfermentemia with alanine aminotransferase and aspartate aminotransferase values exceeding two times but less than five times the upper limit of normal, and alanine aminotransferase and aspartate aminotransferase values exceeding five times the upper limit of normal, developed in 3 (15.7 %) of children, which required a change in the dose and duration of prednisone administration. Thrombocytopenia developed in patients at the preclinical and manifest stages of SMA in 4 (21.0 %) and 11 (57.8 %) cases, respectively. Platelet count normalization occurred in the period from 2 to 4 weeks. Troponin I was detected in 10 (52.6 %) children aged 2–8 weeks with less than a twofold increase in the upper limit of normal and decreased with prednisone maintenance doses. All deviations of laboratory parameters had different periods of normalization – from 10 days to 11 months. At the same time, there was no significant clinical deterioration requiring the transfer of patients to the intensive care unit.

Conclusion. The use of OA for the treatment of SMA 5q with 2 or 3 copies of the SMN2 gene at preclinical and manifest stages of the disease in children aged 1 to 34 months demonstrates high efficacy and an acceptable safety profile. Obtaining optimal results is determined by the clinical manifestations at the time of gene replacement therapy and the comorbid background.

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