Experience of using gene replacement therapy with Zolgensma® (onasemnogene abeparvovec) in real clinical practice in Russia

Abstract

Objective: to analyze the safety and evaluate the effectiveness of therapy with onasemnogene abeparvovec in patients with spinal muscular atrophy in real clinical practice based on the experience of using the drug in the neuromuscular center of Research Clinical Pediatric Institute of Pirogov Russian National Research Medical University.Materials and methods. Patients with spinal muscular atrophy received therapy with onasemnogene abeparvovec based on the prescription of the drug according to vital indications by a council of physicians of Federal institutions (the availability of the drug was carried out within the framework of the MAP Program (global program of managed access MAP to AVXS-101 for eligible patients in countries, where it is not approved by regulatory authorities (NCT03955679), through funding from the charitable foundations, as well as through funding from the state fund “Circle of Kindness”. The drug tolerance was assessed and the analysis of side effects after drug administration was based on the criteria for adverse events (General criteria Adverse Event Terminology (CTCAE) v. 5.0) Patient motor function was assessed prior to treatment initiation and every 3–6 months after therapy using the Philadelphia Pediatric Hospital’s CHOP INTEND scale, total motor development based on Hammersmith Hospital Neurological Assessment Scale in Young Children, Part 2 (HINE-2), and the acquisition of new motor skills.Results. 41 children aged 5 to 47 months (weighing no more than 21 kg) received therapy with onasemnogene abeparvovec in the period from April 2020 to December 2021. Adverse events (hyperthermia, decreased appetite, nausea, vomiting) were registered in all patients with different degree of severity. Elevated levels of transaminases greater than 2 times the upper limit of the normal range were observed in 32 patients (78 %), thrombocytopenia in 9 patients (22 %). 15 patients (36 %) required a dose adjustment of corticosteroids.17 patients underwent assessment of motor scales after 6 months, 10 children were assessed after a year. The average improvement on the HINE-2 scale was 3.3 / 4.4 points, respectively. The average improvement on the CHOP INTEND Scale was 7.1 / 9.4 points after 6 / 12 months of therapy.Conclusion. The efficacy and safety of onasemnogene abeparvovec have been demonstrated in real clinical practice in the treatment of spinal muscular atrophy for children in different age groups with a body weight of no more than 21 kg.

Keywords

• spinal muscular atrophy
• onasemnogene abeparvovec
• zolgensma®
• safety
• map program
• increased transaminases
• smn1 gene
• gene replacement therapy