Saute Jonas Alex, Muntadas Javier, Gurgel-Giannetti Juliana, Monges Soledad, Aliberti Paula, Mendonça Rodrigo Holanda, Alecu Iulian, Ritter Shannon, Martins de Lana Janaina, Mumneh Nayla, Zanoteli Edmar
Medical Genetics Service, Hospital de Clinicas de Porto Alegre, Av Ramiro Barcelos, 2350, Santa Cecelia, Porto Alegre, RS, 90035-903, Brazil.
Internal Medicine Department, Universidade Federal do Rio Grande do Sul, Av. Paulo Gama, 110 - Bairro Farroupilha, Porto Alegre, RS, 90010-150, Brazil.
Lancet Reg Health Am. 2025 Jul 28;49:101193. doi: 10.1016/j.lana.2025.101193. eCollection 2025 Sep.
OFELIA aimed to evaluate outcomes related to safety and motor milestones following administration of onasemnogene abeparvovec, a one-time gene replacement therapy, for patients with spinal muscular atrophy (SMA) from Latin America.
OFELIA (NCT05073133) is a phase 4, 18-month, open-label, multicenter, non-randomised study (Brazil, Argentina) of onasemnogene abeparvovec treatment (1·1 × 10 vg/kg) for symptomatic patients with SMA ≤24 months of age and ≤17 kg (grouped by age [0-12 vs >12-24 months] and weight [<8·5 kg vs ≥8·5 kg]). The primary endpoint was safety. The secondary endpoint was demonstration of motor milestones measured at screening and at 6, 12, and 18 months post-onasemnogene abeparvovec infusion, according to the World Health Organization Multicentre Growth Reference Study criteria.
Sixteen patients were enrolled (n = 11/16 female; n = 10/16 SMA type 1) (n = 17 screened). All reported adverse events (AEs). Eleven reported serious AEs; 12 reported an AE of special interest, most commonly hepatotoxicity (asymptomatic) (n = 11/12), thrombocytopenia (n = 5/12), and thrombotic microangiopathy (n = 2/12). Two deaths occurred: one possibly related to treatment (AST >20 × upper limit of normal, sepsis, infection, multiorgan failure, thrombotic microangiopathy) and one due to respiratory infection. Most patients maintained/improved motor milestones up to 18 months post-onasemnogene abeparvovec (e.g., sitting, crawling, standing, walking), including those in the >12-24-month age group.
Most common AEs of special interest were hepatotoxicity, thrombocytopenia, and thrombotic microangiopathy; incidence rates (hepatotoxicity, thrombocytopenia) were similar compared with studies in patients >6 months of age and >8·5 kg. Efficacy data on demonstration of motor milestones suggest that Latin American patients with SMA may benefit from onasemnogene abeparvovec treatment.
The study was funded by Novartis Pharma AG, Basel, Switzerland.
OFELIA旨在评估一次性基因替代疗法onasemnogene abeparvovec用于拉丁美洲脊髓性肌萎缩症（SMA）患者后与安全性和运动里程碑相关的结果。
OFELIA（NCT05073133）是一项为期18个月的4期开放标签多中心非随机研究（巴西、阿根廷），研究对象为年龄≤24个月且体重≤17千克的有症状SMA患者，接受onasemnogene abeparvovec治疗（1.1×10 vg/kg）（按年龄[0至12个月对比>12至24个月]和体重[<8.5千克对比≥8.5千克]分组）。主要终点是安全性。次要终点是根据世界卫生组织多中心生长参考研究标准，在筛查时以及onasemnogene abeparvovec输注后6个月、12个月和18个月测量运动里程碑。
共纳入16名患者（16名中有11名女性；16名中有10名是1型SMA）（17名接受筛查）。所有患者均报告了不良事件（AE）。11名患者报告了严重AE；12名患者报告了特别关注的AE，最常见的是肝毒性（无症状）（12名中有11名）、血小板减少症（12名中有5名）和血栓性微血管病（12名中有2名）。发生了2例死亡：1例可能与治疗有关（谷草转氨酶>正常上限20倍、败血症、感染、多器官功能衰竭、血栓性微血管病），1例死于呼吸道感染。大多数患者在onasemnogene abeparvovec治疗后18个月内保持/改善了运动里程碑（如坐、爬、站、走），包括12至24个月年龄组中的患者。
特别关注的最常见AE是肝毒性、血小板减少症和血栓性微血管病；与6个月以上且体重>8.5千克患者的研究相比，其发生率（肝毒性、血小板减少症）相似。运动里程碑的疗效数据表明，拉丁美洲的SMA患者可能从onasemnogene abeparvovec治疗中获益。
该研究由瑞士巴塞尔的诺华制药有限公司资助。
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