Suzuki Mari, Jeng Linda J B, Chefo Solomon, Wang Yan, Price Dionne, Li Xiaohui, Wang Jie, Li Ruo-Jing, Ma Lian, Yang Yuching, Zhang Xinyuan, Zheng Nan, Zhang Ke, Joseph David B, Shroff Hitesh, Doan Jenny, Pacanowski Michael, Smpokou Patroula, Donohue Kathleen, Joffe Hylton V
Office of New Drugs, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD.
Office of New Drugs, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD.
Genet Med. 2023 Feb;25(2):100335. doi: 10.1016/j.gim.2022.11.003. Epub 2022 Dec 12.
The U.S. Food and Drug Administration recently approved lonafarnib as the first treatment for Hutchinson-Gilford progeria syndrome (HGPS) and processing-deficient progeroid laminopathies. This approval was primarily based on a comparison of patients with HGPS treated with lonafarnib in 2 open-label trials with an untreated patient cohort. With up to 11 years of follow-up, it was found that the lonafarnib treated patients with HGPS had a survival benefit of 2.5 years compared with the untreated patients with HGPS. This large treatment effect on the objective endpoint of mortality using a well-matched comparator group mitigated potential sources of bias and together with other evidence, established compelling evidence of a drug effect with benefits that outweighed the risks. This approval is an example of U.S. Food and Drug Administration's regulatory flexibility for a rare disease while ensuring that standards for drug approval are met.
美国食品药品监督管理局最近批准洛那法尼用于治疗哈钦森-吉尔福德早衰综合征（HGPS）及加工缺陷型早老样核纤层蛋白病，这是首个获此批准的疗法。该批准主要基于两项开放标签试验中接受洛那法尼治疗的HGPS患者与未经治疗的患者队列的对比。经过长达11年的随访，发现接受洛那法尼治疗的HGPS患者与未经治疗的HGPS患者相比，有2.5年的生存获益。使用匹配良好的对照组对死亡率这一客观终点产生的巨大治疗效果减轻了潜在的偏倚来源，并与其他证据一起，确立了令人信服的药物疗效证据，其益处大于风险。该批准是美国食品药品监督管理局在确保满足药物批准标准的同时，对罕见病采取监管灵活性的一个范例。
