P.104 Treatments and outcomes for patients with spinal muscular atrophy (SMA) type 2: Findings from RESTORE registry

Abstract

We aimed to describe real-world treatment patterns/outcomes for patients with SMA type 2 (SMA2). RESTORE is an ongoing SMA patient registry. We analyzed changes in motor milestones and disability scores and assessed treatment-emergent adverse events (TEAEs) for patients who received ≥1 disease-modifying therapy (DMT; gene therapy [onasemnogene abeparvovec (OA)] or SMN2 modulator [nusinersen/risdiplam]). As of Nov. 23, 2021, RESTORE included 48 patients with SMA2, and 29 (60.4%) were female. Eight (16.7%), 37 (77.1%), 2 (4.2%) and 1 (2.1%) had 2, 3, 4 and ≥4 SMN2 gene copies, respectively. Median age at SMA diagnosis was 14.0 months and at first DMT administration, 16.0 months. Median interval between diagnosis and first DMT was 1 month. Median age at first DMT differed between groups (p=0.0033): OA monotherapy, 16.5 months (n=24); nusinersen monotherapy, 25 months (n=10); risdiplam monotherapy, 8 months (n=1); switching from other DMT to OA, 12 months (n=11); and receiving add-on therapy to OA, 15.5 months (n=2). Of 26 patients with ≥2 motor milestone assessments (≥1 post-DMT administration), all but 4 (OA only [n=3], nusinersen only [n=1]) maintained or achieved new milestones: 13 (59.1%) received OA monotherapy; 6 (27.3%) switched from nusinersen to OA; 1 (4.5%) received add-on to OA; and 2 (9.1%) received nusinersen only. Median HFMSE score change was 5.5 (n=10), with median monthly change of 0.6 (n=10) for all patients, and 11.0 (n=5), with median monthly change of 0.7 (n=6) for patients receiving OA monotherapy. Any-grade TEAEs were recorded for 12/24 (50%) patients who received OA monotherapy, 7/11 (63.6%) who switched from nusinersen to OA, and 1/2 (50%) who received add-on treatment to OA. Of patients who received OA, 3 required non-oral feeding support and 2 required BiPAP ventilation. AEs in RESTORE are consistent with OA experience. No new safety signals were identified. OA is effective and has an acceptable safety profile for patients with SMA2.