Safety and Tolerability of Onasemnogene Abeparvovec for Patients with Spinal Muscular Atrophy Weighing ≤17 kg and ≤24 Months Old: Phase 4 OFELIA Study


Clinical Trials

Poster Number: S120


Jonas Saute, Medical Genetics Service, Hospital de Clinicas de Porto Alegre, Javier Muntadas, MD, Hospital Italiano de Buenos Aires, Juliana Gurgel-Gianetti, MD, Universidade Federal de Minas Gerais, Soledad Monges, MD, Hospital de Pediatría S.A.M.I.C. “Prof. Dr. Juan P. Garrahan,” Buenos Aires, Paula Aliberti, PhD, Novartis, Iulian Alecu, MD, Novartis Pharmaceuticals, Shannon Ritter, MS, Novartis Gene Therapies, Inc., Janaina de Lana, MD, Novartis Biociências S.A. Pharma, Nayla Mumneh, MD, Novartis, Edmar Zanoteli, MD, PhD, Hospital de Clinicas da Faculdade de Medicina da Universidade de São Paulo (HCFMUSP)

Background: Intravenous (IV) onasemnogene abeparvovec (OA) demonstrated efficacy and safety for patients with spinal muscular atrophy (SMA), but, at the initiation of OFELIA (NCT05073133), clinical trials had only enrolled patients weighing ≤8.5 kg and ≤9 months old. OFELIA was a phase 4, open-label, multicenter study conducted in Latin America that enrolled patients with symptomatic SMA weighing ≤17 kg.
Objective: OFELIA assessed safety and efficacy of single-dose IV OA for patients weighing ≤17 kg and ≤24 months old over 18 months post-infusion. Primary endpoint was safety, measured by treatment-emergent adverse events (TEAEs), serious TEAEs, adverse events of special interest (AESIs), and hematology/laboratory changes. Secondary endpoint was efficacy, measured by World Health Organization–Multicenter Growth Reference Study (WHO-MGRS) motor milestone achievement. Data were summarized descriptively.
Results: Sixteen patients were enrolled; three (19%) were previously treated with nusinersen. At dosing, median (range) age was 17.88 (3.95–23.75) months and weight was 8.35 (6.10–12.10) kg. Most patients had SMA type 1 (n=10; 62.5%) and two (n=8; 50.0%) or three (n=8; 50.0%) SMN2 copies. Safety was consistent with previous studies with OA. Eleven (68.8%) patients experienced serious TEAEs. Twelve (75.0%) patients experienced AESIs: 11 (91.7%) hepatotoxicity, 5 (41.7%) thrombocytopenia, and 2 (16.7%) thrombotic microangiopathy (TMA). Transaminase elevations (n=2/16; 12.5%) were asymptomatic; troponin elevations (n=6/8; 75.0%) were isolated and without clinical relevance. Two (12.5%) deaths occurred: one due to AESI of TMA (related to treatment per investigator); the second death was not related to treatment. Patients received a median (range) post-infusion corticosteroid dose of 0.90 (0.10–2.00) mg/kg for a median (range) of 183.50 (11.00–600.00) days. Most patients achieved WHO-MGRS motor milestones by 18 months of follow-up (up to 3 years old for most patients): sitting without support (n=10/12; 83.3%), crawling (n=3/12; 25.0%), standing with assistance (n=7/12; 58.3%), walking with assistance (n=2/12; 16.7%), standing alone (n=3/12; 25.0%), and walking alone (n=1/12; 8.3%).
Conclusions: OFELIA confirms that OA is safe and efficacious for older, heavier patients with SMA and for patients from different geographic locations than previously studied. Most patients demonstrated maintenance or improvement of motor milestones up to 18 months post-treatment.