Patterns of Troponin I Elevations in Patients with SMA Treated with Onasemnogene Abeparvovec: Real-World Findings from the RESTORE Registry


Clinical Management

Poster Number: S96


Matthew Harmelink, MD, Medical College of Wisconsin, Laurent Servais, MD, PhD, University of Oxford, Nancy Bass, MD, Children's Wisconsin, Medical College of Wisconsin, 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, Dheeraj Raju, PhD, Novartis Gene Therapies, Inc., Iulian Alecu, MD, Novartis Pharmaceuticals, Farid Khan, MD, Novartis Gene Therapies, Inc., Kamal Benguerba, MD, Novartis Gene Therapies Switzerland GmbH, Sandra Reyna, MD, Novartis, Richard Finkel, MD, St. Jude Children’s Research Hospital

Background: Onasemnogene abeparvovec (OA), a one-time, adeno-associated-virus–based gene replacement therapy, has established efficacy for treatment of spinal muscular atrophy (SMA), a rare genetic neuromuscular disease. Isolated asymptomatic troponin elevations were noted in some OA clinical trial participants, and based primarily on preclinical findings, cardiac troponin monitoring is currently indicated per OA product labeling (FDA recommending six post-infusion measurements). However, the etiology of these troponin elevations and implications for cardiotoxicity in humans are unclear.
Objective: To describe patterns of troponin I elevations and cardiac adverse events in patients with SMA treated with OA (alone or with other SMA treatments) enrolled in RESTORE, a multinational, noninterventional SMA registry.
Methods: Patients with troponin I elevations were identified by screening adverse events suspected due to OA reported in the RESTORE database. For this analysis, elevation was defined as ≥0.04 ng/mL.
Results: As of May 23, 2023, 21/383 (5.5%) patients in RESTORE had ≥one troponin I elevation reported as an OA-related adverse event. Nine patients received nusinersen before OA infusion. Median age at OA infusion was 3 months (range, 0–20 months). Of 13 patients with pre-infusion measurements, troponin I was elevated in four (30.8%). Post-infusion elevations ranged as high as ~13× ULN and elevations ≥2× ULN were recorded for nine of 21 patients (42.9%). Troponin I elevations resolved in all cases and recovery was observed by the second assessment after initial elevation in the majority of cases. Other cardiac adverse events were reported in 20/383 patients (5.2%), none associated with elevated troponin I.
Conclusions: Troponin I elevations observed in OA-treated patients in RESTORE appear to be transient and self-limiting and were not associated with clinically concerning cardiac adverse events. While cardiac events may occur in patients with SMA due to the underlying disease process, these real-world findings do not suggest an immediate cardiotoxicity of OA.