Risdiplam Add-On Therapy Following Onasemnogene Abeparvovec in Children With Spinal Muscular Atrophy and 2 SMN2 Copies: A Multi-Center Case Series.

INTRODUCTION/

aimsThree disease-modifying therapies are approved for individuals with spinal muscular atrophy (SMA); however, data concerning the combination of these therapies remain limited. This study aimed to evaluate the safety and efficacy of add-on risdiplam in children who had experienced clinical deterioration despite gene therapy with onasemnogene abeparvovec.

methodsThis is a retrospective case series study at two centers of children treated with risdiplam who had previously received onasemnogene abeparvovec. Therapy was evaluated by clinical examination, standardized physiotherapeutic assessments, and parent perspectives.

resultsFive patients with SMA (four male and one female), diagnosed between 0 and 8 months, were included in the study. All had 2 SMN2 copies and were started on risdiplam between five and 48 months after onasemnogene abeparvovec. Risdiplam was added due to motor regression, dysphagia, new onset of respiratory insufficiency, and/or recurrent pneumonias. Four children showed improvements in motor development, swallowing, and respiratory function. One child remained stable. Parents perceived a significant improvement in general impression, motor, and respiratory function. The add-on therapy was well tolerated without adverse events. DISCUSSION: Our results indicate an improvement in most children in a case series through add-on risdiplam. Evaluating clinical outcome parameters in clinical practice may prove challenging and should be complemented by the parental perspective. The decision regarding the use of add-on therapy in children with SMA who receive one line of treatment but show a clinical deterioration should be considered on an individual level, and assessments of predefined therapeutic goals are recommended.