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Abstract：
Primary demyelinating disorders of the central nervous system (CNS) include multiple sclerosis and the orphan conditions neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein IgG-associated disease (MOGAD). Curative technologies under development aim to selectively block autoimmune reactions against specific autoantigens while preserving the responsiveness of the immune system to other antigens. Our analysis focused on target patient selection for such developments, carefully considering the relevant clinical, regulatory, and market-related aspects. We found that the selection of patients with orphan conditions as target populations offers several advantages. Treatments for orphan conditions are associated with limited production capacity, qualify for regulatory incentives, and may require significantly shorter and lower-scale clinical programs. Furthermore, they may meet a higher acceptable cost-effectiveness threshold in order to compensate for the low numbers of patients to be treated. Finally, curative technologies targeting orphan indications could enter less competitive markets with lower risk of generic price erosion and would benefit from additional market protection measures available only for orphan products. These advantages position orphan conditions and subgroups as the most attractive target indications among primary demyelinating disorders of the CNS. The authors believe that after successful proof-of-principle demonstrations in orphan conditions, broader autoimmune patient populations may also benefit from the success of these pioneering developments.
摘要：
中枢神经系统（CNS）的原发性脱髓鞘疾病包括多发性硬化症和孤儿性视神经脊髓炎谱系障碍（NMOSD）和髓鞘少突胶质细胞糖蛋白IgG相关疾病（MOGAD）。正在开发的治疗技术旨在选择性地阻断针对特定自身抗原的自身免疫反应，同时保留免疫系统对其他抗原的反应性。我们的分析重点是针对此类发展的目标患者选择，仔细考虑相关的临床，监管,以及与市场相关的方面。我们发现，选择孤儿患者作为目标人群具有多种优势。孤儿状况的治疗与有限的生产能力有关，有资格获得监管激励，并且可能需要明显较短和较低规模的临床计划。此外，它们可能达到较高的可接受的成本-效果阈值,以弥补需要治疗的患者数量少.最后,针对孤儿适应症的治疗技术可以进入竞争较弱的市场，仿制药价格下降的风险较低，并将受益于仅适用于孤儿产品的额外市场保护措施。这些优势将孤儿病和亚组定位为CNS原发性脱髓鞘疾病中最有吸引力的目标适应症。作者认为，在孤儿条件下成功地进行了原理证明，更广泛的自身免疫患者群体也可能受益于这些开创性进展的成功.
