Valerieva Anna, Caballero Teresa, Magerl Markus, Frade Joao P, Audhya Paul K, Craig Timothy
Department of Allergology, Medical University of Sofia, University Hospital "Alexandrovska", Sofia, Bulgaria.
Servicio de Alergia, Hospital Universitario la Paz, IdiPAZ, CIBERER U754, Madrid, Spain.
Clin Transl Allergy. 2024 Sep;14(9):e12391. doi: 10.1002/clt2.12391.
Hereditary angioedema (HAE) is a rare genetic disorder characterized by unpredictable, debilitating episodes of submucosal and/or subcutaneous tissue swelling, which may be life-threatening depending on anatomic location. The two primary management strategies for HAE are ready access to effective on-demand treatment in all patients and the prevention of attacks (short-term prophylaxis [STP] and long-term prophylaxis [LTP]) in appropriate patients. All approved on-demand and most LTP medications require subcutaneous or intravenous administration. Injection-related challenges include trypanophobia (fear of needles), difficulty with self-administration, injection-site reactions (e.g., pain, erythema, bleeding, bruising), and anxiety-all contributing to poor compliance and administration delays. Oral HAE treatments may improve outcomes by reducing treatment barriers.
To review oral therapies, approved or in development, for on-demand treatment and/or prevention of HAE attacks.
To provide a comprehensive review, data was obtained from publicly available resources through a targeted PubMed literature review and supplemented by information provided on company websites (search cutoff of May 31, 2024).
Berotralstat, an oral plasma kallikrein (PKa) inhibitor, is approved for LTP. Sebetralstat, another PKa inhibitor, is the investigational first oral on-demand HAE treatment to complete a phase 3 trial. Deucrictibant, an oral bradykinin B2 receptor antagonist, has completed phase 2 trials for on-demand therapy and LTP. Several other oral PKa inhibitors (ATN249, VE-4666, and VE-4062) are in early development for LTP.
Substantial advances have been made in the development of oral treatments for HAE. These treatments have the potential to improve and optimize clinical outcomes, satisfaction, and quality of life among patients with HAE.
遗传性血管性水肿（HAE）是一种罕见的遗传性疾病，其特征是黏膜下和/或皮下组织肿胀发作不可预测且使人衰弱，根据解剖位置不同，可能危及生命。HAE的两种主要治疗策略是确保所有患者都能随时获得有效的按需治疗，以及对合适的患者进行发作预防（短期预防[STP]和长期预防[LTP]）。所有获批的按需治疗药物和大多数LTP药物都需要皮下或静脉注射给药。与注射相关的问题包括恐针症（害怕打针）、自我给药困难、注射部位反应（如疼痛、红斑、出血、瘀伤）和焦虑，所有这些都会导致依从性差和给药延迟。口服HAE治疗可能通过减少治疗障碍来改善治疗效果。
综述已获批或正在研发的用于按需治疗和/或预防HAE发作的口服疗法。
为提供全面的综述，通过有针对性的PubMed文献综述从公开可用资源中获取数据，并辅以公司网站提供的信息（检索截止日期为2024年5月31日）。
口服血浆激肽释放酶（PKa）抑制剂贝罗司他获批用于LTP。另一种PKa抑制剂塞贝司他是首个完成3期试验的口服按需治疗HAE的研究性药物。口服缓激肽B2受体拮抗剂德克里班已完成按需治疗和LTP的2期试验。其他几种口服PKa抑制剂（ATN249、VE - 4666和VE - 4062）正处于LTP的早期研发阶段。
HAE口服治疗的研发取得了重大进展。这些治疗方法有可能改善和优化HAE患者的临床疗效、满意度和生活质量。
