Deesker Lisa J, Franssen Casper F M, Dorresteijn Eiske, van de Kar Nicole C A J, Nurmohamed S Azam, Severs David, Garrelfs Sander F, Pisters-van Roy Anke A M G, Hollak Carla E M, Groothoff Jaap W
Department of Pediatric Nephrology, Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
Department of Nephrology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Nephrol Dial Transplant. 2025 Sep 29;40(10):1887-1896. doi: 10.1093/ndt/gfaf060.
In search for controlled access to expensive innovative orphan drugs, a national access route called 'Orphan Drug Access Protocol' (ODAP) was developed and piloted with lumasiran, a new drug for patients with primary hyperoxaluria type 1 (PH1). Here, we present a 2-year evaluation of this pilot study.
Specialists from the Dutch PH1 Expert Centre and the national ODAP steering group developed a protocol for controlled and conditional treatment of children and adults with PH1 with lumasiran. Indication for treatment is based on specific clinical characteristics. Cessation or continuation of therapy is evaluated every 6 months for 5 years by a national indication committee consisting of PH1 specialists, based on biochemical and clinical response. Drug wastage is minimized by centralizing and pooling patients for administration.
Between September 2022 and September 2024, 21 PH1 patients were reviewed and 76% were deemed eligible for lumasiran treatment. Ten patients were already receiving lumasiran through clinical trials or early access programs at time of assessment. The follow-up time with lumasiran was 0.1-6.6 years, including trial years. All patients with >1 year lumasiran treatment responded significantly biochemically and clinically. Details on outcomes are presented. Denials for lumasiran therapy were nearly all based on full pyridoxine responsiveness. All denied patients, except one, had good clinical outcomes. This patient received lumasiran after initial denial based on clinical and biochemical course. Patient selection and minimizing wastage saved approximately €3 227 065 per year based on the official list price.
This national ODAP protocol enabled access to lumasiran therapy for severely ill patients, prevented unnecessary treatment in others, and provided new insights into the real-world effectiveness of lumasiran in PH1 patients through systematic monitoring. It may serve as a template for future access routes to new expensive therapeutics in orphan diseases.
为寻求对昂贵的创新孤儿药进行可控获取，开发了一种名为“孤儿药获取协议”（ODAP）的国家获取途径，并在用于1型原发性高草酸尿症（PH1）患者的新药鲁马西拉上进行了试点。在此，我们展示了这项试点研究的两年评估结果。
荷兰PH1专家中心和国家ODAP指导小组的专家制定了一项使用鲁马西拉对儿童和成人PH1患者进行可控和有条件治疗的方案。治疗指征基于特定的临床特征。由PH1专家组成的国家指征委员会每6个月对治疗的停止或继续进行5年的评估，评估基于生化和临床反应。通过集中和汇集患者进行给药，将药物浪费降至最低。
在2022年9月至2024年9月期间，对21名PH1患者进行了评估，76%的患者被认为符合鲁马西拉治疗条件。在评估时，有10名患者已经通过临床试验或早期获取项目接受鲁马西拉治疗。鲁马西拉的随访时间为0.1至6.6年，包括试验年份。所有接受鲁马西拉治疗超过1年的患者在生化和临床方面均有显著反应。给出了结果详情。鲁马西拉治疗被拒绝几乎全部基于对吡哆醇的完全反应性。除一名患者外，所有被拒绝的患者临床结局良好。该患者在最初基于临床和生化过程被拒绝后接受了鲁马西拉治疗。基于官方标价，患者选择和减少浪费每年节省了约3227065欧元。
这项国家ODAP方案使重症患者能够获得鲁马西拉治疗，防止了其他患者的不必要治疗，并通过系统监测为鲁马西拉在PH1患者中的实际疗效提供了新见解。它可能成为未来孤儿病新的昂贵治疗方法获取途径的模板。
