s of the 51st Workshop for Pediatric Research 51st Workshop for Pediatric Research Gottingen, Germany 16-17 April 2015 This supplement has not been sponsored. Meeting abstracts Aims We asked the research question, how many orphan drugs were intended to be developed in the area of rare rheumatologic diseases (RRDs) and lysosomal storage disorders (LSDs), measured as the number of orphan drug designations at the FDA between 1983 and 2013. In addition, we analyzed the technology platforms and factors for successful registration. Methods Analysis of the FDA database for orphan drug designations. Results RRDs in the last three decades, out of 77 orphan drug designations, 14 FDA orphan drug approvals were granted for RRDs, i.e. juvenile idiopathic arthritis (N = 5), cryoporin associated periodic syndromes (N = 3), uveitis (N = 3), familial Mediterranean fever (N = 1), anti-neutrophil cytoplasmic antibody-associated vasculitis (N = 1), xerostomia/ keratoconjunctivitis sicca in Sjogren's syndrome (N = 1). Mean time (SD) from designation to approval was 3.9 (2.81) years. 6/14 FDA-approved drugs were small molecules, 8/14 were biologics. 15/77 orphan drug designations were withdrawn. Despite the rarity of conditions, 13/14 pivotal studies were randomized controlled trials. LSDs: Orphan drug status was designated 70 times for 20 conditions. Fourteen drugs for seven conditions received FDA approval. Orphan drug status was designated for enzymes, modified enzymes, fusion proteins, chemical chaperones, small molecules, stem cells and gene therapies. Approved therapies were enzyme replacement (N = 10), substrate reduction (N = 1), and small molecules (N = 3). FDA approval was statistically significantly associated with a disease prevalence ≥ 0.5/100,000 (P =.007) and clinical development programs that did not require a primary neurological endpoint (P < .001). Conclusions During the last three decades, 14/77 orphan drug designations were approved for the treatment of RRDs. Likewise, 14/70 orphan drug designations were approved for LSDs. Pivotal studies were small clinical trials. These data provide an insight into the drug pipeline and abandoned pathways.

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新型孤儿药和废弃途径——1983 年美国孤儿药法案及其对罕见风湿病和溶酶体贮积症的影响

第 51 届儿科研究研讨会第 51 届儿科研究研讨会，德国哥廷根 2015 年 4 月 16 日至 17 日 本增刊尚未获得赞助。会议摘要 目的 我们提出了一个研究问题，即计划在罕见风湿病 (RRD) 和溶酶体贮积症 (LSD) 领域开发多少孤儿药，以 1983 年至 1983 年间 FDA 指定的孤儿药数量来衡量2013. 此外，我们分析了成功注册的技术平台和因素。方法 分析 FDA 数据库中的孤儿药名称。结果 过去 30 年的 RRD，在 77 个孤儿药指定中，有 14 个 RRD 获得 FDA 孤儿药批准，即幼年特发性关节炎（N = 5）、冷孔蛋白相关周期性综合征（N = 3）、葡萄膜炎（N = 3） ), 家族性地中海热（N = 1）、抗中性粒细胞胞浆抗体相关血管炎（N = 1）、干燥综合征中的口干症/干燥性角结膜炎（N = 1）。从指定到批准的平均时间 (SD) 为 3.9 (2.81) 年。6/14 FDA 批准的药物是小分子药物，8/14 是生物制剂。15/77 孤儿药指定被撤回。尽管条件罕见，但 13/14 的关键研究是随机对照试验。LSD：针对 20 个条件指定了 70 次孤儿药状态。用于 7 种情况的 14 种药物获得 FDA 批准。孤儿药状态被指定为酶、修饰酶、融合蛋白、化学伴侣、小分子、干细胞和基因疗法。批准的疗法是酶替代 (N = 10)、底物减少 (N = 1) 和小分子 (N = 3)。FDA 批准与疾病患病率 ≥ 0.5/100,000 (P = .007) 和不需要主要神经学终点的临床开发计划 (P < .001) 显着相关。结论 在过去的 30 年中，14/77 孤儿药指定被批准用于治疗 RRD。同样，14/70 孤儿药指定被批准用于 LSD。关键研究是小型临床试验。这些数据提供了对药物管道和废弃途径的深入了解。14/70 孤儿药指定被批准用于 LSD。关键研究是小型临床试验。这些数据提供了对药物管道和废弃途径的深入了解。14/70 孤儿药指定被批准用于 LSD。关键研究是小型临床试验。这些数据提供了对药物管道和废弃途径的深入了解。