Treatments and Outcomes for Patients with Spinal Muscular Atrophy Type 2: Findings from RESTORE Registry
Laurent Servais1, Kamal Benguerba2, Darryl C. De Vivo3, Jan Kirschner4, Francesco Muntoni5, Crystal Proud6, Eduardo Tizzano7, Susana Quijano-Roy8, Isabelle Desguerre9, Kyoko Saito10, Dheeraj Raju11, Nicole LaMarca11, Rui Sun11, Fred Anderson12, Eric Faulkner11, Richard Finkel13
1University of Oxford, 2Novartis Gene Therapies Switzerland GmbH, 3Departments of Neurology and Pediatrics, Columbia University Irving Medical Center, 4Clinic for Neuropediatrics and Muscle Disease, University Medical Center Freiburg, 5The Dubowitz Neuromuscular Centre, University College London, Great Ormond Street Institute of Child Health & Great Ormond Street Hospital and National Institute of Health Research, Great Ormond Street Hospital Biomedical Research Centre, 6Children’s Hospital of The King’s Daughters, 7Department of Clinical and Molecular Genetics, Hospital Valle Hebron, 8Garches Neuromuscular Reference Center (GNMH), APHP Raymond Poincare University Hospital (UVSQ Paris Saclay), 9Hôpital Necker Enfants Malades, APHP, 10Institute of Medical Genetics, Tokyo Women’s Medical University, 11Novartis Gene Therapies, Inc., 12Center for Outcomes Research, University of Massachusetts Medical School, 13St. Jude Children's Research Hospital
Objective:
We sought to describe real-world treatment patterns and outcomes for patients with SMA type 2 (SMA2) receiving onasemnogene abeparvovec (OA) monotherapy or who switched to OA from nusinersen.
Background:
Real-world data describing treatment patterns and outcomes for patients with SMA2 are limited. Patients with untreated SMA2 typically have clinically identifiable disease symptoms between 6–18 months of age, and are able to sit independently, but are unable to walk without support.
Design/Methods:
RESTORE is an ongoing SMA patient registry that captures patient data from a variety of sources. We analyzed changes in motor milestones and motor function scores and assessed treatment-emergent adverse events (TEAEs) for patients who received OA monotherapy or switched to OA from nusinersen.
Results:
As of Nov. 23, 2021, 34 patients with SMA2 were identified. Six (17.7%), 27 (79.4%), and 1 (2.9%) had two, three, or four SMN2 gene copies, respectively. Median age at SMA diagnosis was 13.0 months. Age at first DMT administration was 14.0 months. Median interval between diagnosis and first DMT was 1 month. Two-thirds (n=23/34) of patients received OA monotherapy; 11 patients switched to OA from nusinersen. Of 23 patients with ≥2 motor milestone assessments (≥1 post-DMT administration), all but three (OA only [n=3]) maintained or achieved new milestones: 14 (60.9%) received OA monotherapy and six (26.1%) switched to OA from nusinersen. Ten of 11 (90.9%) patients evaluable for CHOP INTEND improved/maintained score, with eight (72.7%) achieving a ≥4-point increase. Any-stage TEAEs were recorded for 11/23 (47.8%) patients who received OA monotherapy and 7/11 (63.6%) who switched to OA from nusinersen. AEs in RESTORE are consistent with overall OA experience. No new safety signals were identified.
Conclusions:
Real-world data from RESTORE indicate that OA is effective and has an acceptable safety profile for patients with SMA2, regardless of prior treatment with nusinersen.