Risdiplam experience following onasemnogene abeparvovec in individuals with spinal muscular atrophy (SMA): a multicenter case series

Topic:

Clinical Management

Poster Number: T299

Author(s):

Nancy Kuntz, MD, Ann & Robert H. Lurie Children's Hospital, Melissa Svoboda, Department of Pediatrics, The Children's Hospital of San Antonio/Baylor College of Medicine, Carmen Leon, MD, U of Florida, Barry J Byrne, MD, PhD, University of Florida, Jena Krueger, Md, HDVCH, Jennifer Kwon, MD, University of Wisconsin - American Family Children's Hospital, Cory Sieburg, Division of Pediatric Neurology, Department of Neurology, University of Wisconsin-Madison, Diana Castro, Neurology Rare Disease Center

Background

With the availability of multiple disease-modifying therapies and the increase in early diagnosis due to newborn screening, the disease course of SMA is rapidly changing. Individuals with SMA and their caregivers are increasingly requesting information on the combination of approved therapies; however, data are limited, and additional evidence is needed.

Objective

To present real-world outcomes from a multicenter retrospective review of children with SMA who were treated with gene transfer therapy, onasemnogene abeparvovec (OA; ZOLGENSMA®) and subsequently received risdiplam (EVRYSDI®), an orally administered treatment.

Methods

Individuals with a genetically confirmed SMA diagnosis from six neuromuscular centers in the US were included. Demographics, clinical characteristics, adverse events (AEs), respiratory function, swallowing function, and neuromotor scores (at initial diagnosis as well as before and after treatment) were collected. Length of time until treatment, rationale for combination therapy and symptom severity before and after treatment were also evaluated.

Results

Nineteen patients, nine (47.4%) of whom were male, were included. Most had Type 1 SMA (n=16) based on clinical diagnosis, two SMN2 copies (n=15), moderate to severe dysphagia based on clinical assessment (n=10) and required breathing assistance (n=10) at baseline. On average, patients received OA 6 months after diagnosis and received risdiplam 16 months thereafter. Common reasons for starting risdiplam were a lack of improvement or plateau in function (n=12). After receiving risdiplam, six patients showed improvements in both respiratory function and dysphagia. Motor function after risdiplam initiation was assessed, and all 14 patients improved. No significant AEs were observed after risdiplam initiation.

Conclusions

Many children in this case series had additional gains in motor, respiratory and/or bulbar function after risdiplam initiation, with no significant AEs reported. These real-world data provide a greater understanding of risdiplam’s risk–benefit profile after OA and insights into decision-making, challenges and opportunities for combination approaches.