Orui Satoshi, Nozue Haruka, Kobayashi Satoko, Fujioka Masaki, Maekawa Yuriko
Portfolio & Product Strategy Department, Torii Pharmaceutical CO., LTD.
Medical Affairs Department, Torii Pharmaceutical CO., LTD.
Nihon Yakurigaku Zasshi. 2021;156(6):382-390. doi: 10.1254/fpj.21069.
Hereditary angioedema (HAE) is a rare disease that causes serious health problem and affects on quality of life for patient due to recurrent episodes of angioedema in various body such as the skin, larynx, digestive tract, and limbs. Many HAE patients have deficiency or dysfunction of C1 inhibitor, impaired regulation of plasma kallikrein activity and overproduction of bradykinin, resulting in leading to episodes of increased capillary hyper permeability and angioedema. Therapy of HAE consists of on-demand treatment for acute attack and prophylactic treatment by suppressing the onset of acute attack in the short and long term. However, no drug has been approved for long-term prophylaxis in Japan. Berotralstat hydrochloride (ORLADEYO Capsules 150 mg) is an oral, selective plasma kallikrein inhibitor approved for the suppression of the onset of acute attacks in HAE in Japan in January 2021. Preclinical studies demonstrated that Berotralstat is a potent and highly specific inhibitor of human plasma kallikrein activity. Berotralstat suppressed bradykinin production in the HUVEC system. Clinical studies demonstrated that oral administration of Berotralstat to HAE type I or type II patients at a dose of 150 mg once daily showed a reduction of HAE attack rate and clinically significant change in angioedema quality of life score. The most common side effect was gastrointestinal symptoms. In conclusion, preclinical and clinical data indicated that Berotralstat is an effective treatment for long-term prophylactic treatment by suppressing the onset of acute attack in HAE patient and is considered to be a useful treatment option for patients.
遗传性血管性水肿（HAE）是一种罕见疾病，会引发严重的健康问题，并因皮肤、喉部、消化道和四肢等身体各部位反复出现血管性水肿而影响患者的生活质量。许多HAE患者存在C1抑制剂缺乏或功能障碍，血浆激肽释放酶活性调节受损以及缓激肽过度产生，导致毛细血管通透性增加和血管性水肿发作。HAE的治疗包括急性发作的按需治疗以及通过短期和长期抑制急性发作来进行预防性治疗。然而，在日本尚无药物被批准用于长期预防。盐酸贝罗司他（ORLADEYO胶囊150mg）是一种口服的选择性血浆激肽释放酶抑制剂，于2021年1月在日本被批准用于抑制HAE急性发作的发生。临床前研究表明，贝罗司他是一种强效且高度特异性的人血浆激肽释放酶活性抑制剂。贝罗司他在人脐静脉内皮细胞（HUVEC）系统中抑制了缓激肽的产生。临床研究表明，对I型或II型HAE患者每日一次口服150mg贝罗司他可降低HAE发作率，并使血管性水肿生活质量评分出现具有临床意义的变化。最常见的副作用是胃肠道症状。总之，临床前和临床数据表明，贝罗司他通过抑制HAE患者急性发作的发生，是一种有效的长期预防性治疗药物，被认为是患者的一种有用治疗选择。
