P.103 Onasemnogene abeparvovec (OA) treatment outcomes by patient weight at infusion: Initial findings from the RESTORE registry

Abstract

Interventional trials of OA demonstrated safety and efficacy for infants typically weighing <8.5 kg at infusion. We aimed to describe real-world outcomes for patients with SMA according to weight at the time of OA infusion. We compared baseline characteristics, effectiveness (measured by CHOP INTEND), and safety of OA for patients weighing <8.5 kg (Group 1) or ≥8.5 kg (Group 2) at the time of infusion in the RESTORE SMA patient registry. As of Nov. 23, 2021, RESTORE included 221 patients with available data on weight at OA infusion. 165 patients weighed <8.5 kg (Group 1), and 56 weighed ≥8.5 kg (Group 2). More patients in group 1 had 2 SMN2 gene copies (72.7% vs. 42.9% in Group 2), while more patients in group 2 had 3 SMN2 gene copies (48.2% vs. 20.6% in Group 1). A majority in group 1 were diagnosed with SMA type 1 (66.1%) or were presymptomatic (25.5%), and most in group 2 were diagnosed with SMA type 1 (44.6%) or type 2 (39.3%). Most patients in group 1 (105/165; 63.6%) were aged <6 months at infusion, and most in group 2 (53/56; 94.6%) were aged ≥6 months at infusion. Monotherapy with OA was greater in group 1 (60.6%) vs. group 2 (37.5%). Different polytherapy regimens were observed in both groups. Of 75 patients in group 1 who were evaluable for CHOP INTEND, 70 (93.3%) improved/maintained score, and 63 (84.0%) achieved increases of ≥4 points. All 14 evaluable patients in Group 2 improved/maintained score. Eight (57.1%) achieved ≥4-point increases. In group 1, 79/165 (47.9%) patients experienced ≥1 treatment-emergent AEs (TEAEs) of any grade, and 41 (24.8%) reported ≥1 serious AEs. In group 2, TEAEs of any grade were reported in 34/56 (60.7%) patients, and 12 (21.4%) reported ≥1 serious AE. No deaths or unexpected OA-related serious AEs were reported. These results suggest that patients weighing ≥8.5 kg at OA infusion may benefit from treatment. We did not observe a difference in the incidence of TEAEs or serious AEs based on patient weight at OA infusion.