Real-World Outcomes Following Onasemnogene Abeparvovec in Patients with SMA and Invasive Ventilatory Support: Findings from the RESTORE Registry


Clinical Management

Poster Number: S95


Laurent Servais, MD, PhD, Department of Pediatrics, MDUK Oxford Neuromuscular Center, University of Oxford, Perry Shieh, MD, PhD, University of California Los Angeles, Natalie Goedeker, DNP, CPNP, Washington University in St. Louis, Megan A. Waldrop, MD, Nationwide Children's Hospital and Ohio State University Wexner Medical Center, Ryosuke Bo, Kobe University Graduate School of Medicine, Yasemin Erbas, SMA Europe, Dheeraj Raju, PhD, Novartis Gene Therapies, Inc., Kamal Benguerba, MD, Novartis Gene Therapies Switzerland GmbH, Sandra Reyna, MD, Novartis, David Wolff, MS, Novartis, Richard Finkel, MD, St. Jude Children’s Research Hospital

Background: Patients with spinal muscular atrophy (SMA) often require invasive ventilatory support (typically tracheostomy). While onasemnogene abeparvovec (OA), a one-time gene therapy, has demonstrated safety and efficacy for patients with SMA in clinical trials, patients requiring invasive ventilatory support were excluded. Therefore, relatively little is known about treatment outcomes for these patients, who may receive gene therapy in real-world practice.
Objective: To describe outcomes following OA for patients with SMA and tracheostomy in RESTORE, a multinational, noninterventional SMA registry.
Results: As of May 23, 2023, 31 OA-treated patients in RESTORE had tracheostomy (one prior to first treatment, all after OA; two SMN2 copies, n=30; one SMN2 copy, n=1). Four patients (12.9%) were identified by newborn screening; 27 (87.1%) were diagnosed clinically. Patients were treated in the United States (n=21), Japan (n=7), and Greece (n=3). Eight patients received OA monotherapy; 23 patients received other treatments(s) before and/or after OA. Median (range) age at diagnosis, initial treatment, and tracheostomy were 4.0 (0.0–14.0) months, 5.0 (1.0–21.0) months, and 8.1 (2.2–28.3) months, respectively. Of 17 patients with recorded motor milestone data, 13 (76.5%) achieved or maintained motor milestones during the observation period. Similarly, 16/17 (94.1%) demonstrated improvement (n=15) or maintenance (n=1) in CHOP INTEND and all patients with available data demonstrated improvement in HFMSE (5/5; 100%) and HINE-2 (1/1; 100%). Clinically meaningful motor function improvements were recorded for 12 patients. Adverse event data were available for 23 patients; four were serious and treatment-related. Event types were consistent with the established safety profile of OA. Two deaths were recorded, neither related to treatment.
Conclusions: SMA patients who require tracheostomy may be less likely to receive potentially lifesaving treatment. Here, we show that patients with tracheostomy demonstrated improvements after OA (regardless of other treatment[s]) across real-word settings, indicating positive benefit-risk for these children.