Long-Term Real-World Outcomes Following Onasemnogene Abeparvovec Monotherapy for Patients with SMA: Updated Findings from the RESTORE Registry

Topic:

Clinical Trials

Poster Number: 102 S

Author(s):

Laurent Servais, MD, PhD, Department of Pediatrics, MDUK Oxford Neuromuscular Center, University of Oxford, John Day, MD, PhD, Stanford, Darryl C. De Vivo, MD, PhD, Columbia University Irving Medical Center, Janbernd Kirschner, MD, Medical Center-University of Freiburg, Freiburg, Germany, Eugenio M. Mercuri, MD, Pediatric Neurology Institute, Catholic University and Nemo Pediatrico, Rome, Italy, Francesco Muntoni, MD, Dubowitz Neuromuscular Centre, UCL and Great Ormond Street Hospital Trust, London, UK, Crystal Proud, MD, Children’s Hospital of the King’s Daughters, Norfolk, VA, USA, Perry Shieh, MD, University of California Los Angeles, Eduardo F. Tizzano, MD, PhD, Hospital Vall d’Hebron, Susana Quijano-Roy, MD, APHP Raymond Poincaré University Hospital (UVSQ Paris Saclay), Isabelle Desguerre, MD, PhD, Hôpital Necker Enfants Malades, Kayoko Saito, MD, PhD, Tokyo Women’s Medical University, Yasemin Erbas, PhD, SMA Europe, Sandra P. Reyna, MD, Novartis Pharma AG, Iulian Alecu, MD, [email protected], Kamal Benguerba, MD, MSc, Novartis Pharma AG, Dheeraj Raju, MSIE, MS, PhD, Novartis Pharma AG, David Wolff, MS, Novartis Pharma AG, Richard Finkel, MD, St Jude Children's Research Hospital

Background: Previous findings have been reported for patients with spinal muscular atrophy (SMA) treated with onasemnogene abeparvovec (OA), a one-time gene therapy, from the RESTORE registry (mean follow-up, 13.7 months; N=168).
Objectives: Here, we build on long-term safety and effectiveness data for OA monotherapy in a larger RESTORE patient cohort with greater follow-up duration.
Results: Motor function was assessed with Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND), Hammersmith Functional Motor Scale – Expanded (HFMSE), and the Hammersmith Infant Neurological Examination – Section 2 (HINE-2). Of 251 patients (May 23, 2024, data cutoff), median (IQR) ages at SMA diagnosis and OA infusion were 1 (0–6) month and 3 (1–8) months. Median (IQR) time from OA infusion to last visit was 23.6 (14.3–35.7) (range, 0.5–61.6) months. Of 227 patients, 109 (48.0%) had an adverse event (AE); 54 (23.8%) had related AEs, which were serious for seven patients (3.1%). Most common AEs of special interest were hepatotoxicity (n=52, 22.9%), cardiac AEs (n=31, 13.7%), and transient thrombocytopenia (n=28, 12.3%). Six deaths (2.4%) occurred. Overall, most patients demonstrated improvements in motor function scores, with 102 of 115 patients assessed (88.7%) achieving or maintaining CHOP INTEND scores of ≥40 points (achieved, n=33 [28.7%]; maintained, n=69 [60.0%]), with a mean (SD) of 12.9 (10.1) months between assessments. Similarly, 52 of 55 patients assessed (94.5%) achieved or maintained ≥3-point improvements in HFMSE scores (achieved, n=41 [74.5%]; maintained, n=16 [29.1%]). HINE-2 scores also demonstrated progressive increases over time, with 11 patients achieving the maximal score of 26 (SMN2 copies: two [n=3]; three [n=3]; ≥4 [n=5]). Motor function improvements were maintained for up to 5 years.
Conclusions: These data, while limited to OA monotherapy-treated patients, indicate therapeutic benefit for up to 5 years post-dosing, providing further evidence for OA as a durable treatment for SMA patients.