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罕见淋巴瘤新药!BTK 抑制剂 Tirabrutinib 申请上市,治疗原发性中枢神经系统淋巴瘤 (PCNSL)!

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小野制药近日宣布,已在日本提交BTK抑制剂Tirabrutinib hydrochloride (ONO-4059, Tirabrutinib) 用于治疗复发性或难治性原发性中枢神经系统淋巴瘤 (PCNSL) 的制造和销售申请。

此次申请基于一项多中心、开放标签、非对照I/II期研究 (ONO-4059-02) 的结果。该研究共入组了 44 例复发性或难治性 PCNSL 患者,研究中 Tirabrutinib 每日口服一次。今年8月20日,日本卫生劳动福利部 (MHLW) 已授予 Tirabrutinib治疗 PCNSL 的孤儿药资格。

PCNSL 为 B 淋巴细胞来源的一种恶性神经性淋巴瘤,病变通常局限于脑、脊髓和(或)眼睛,很少在中枢神经系统 (CNS)外扩散。PCNSL 患者的体征和症状因病变部位而异,包括局部神经病、神经精神症状、与颅内压升高相关的症状、癫痫、眼部症状、头痛、运动困难、颅神经病和神经根病。

目前,未经治疗的 PCNSL 患者接受大剂量甲氨蝶呤为基础的治疗,随后接受全脑放射治疗,其中部分患者获得长期缓解,但许多患者会复发。还有一些难治性患者对最初的治疗没有反应。对于复发性或难治性PCNSL 患者,尚未建立标准治疗方案,治疗选择也非常有限。因此,对于复发性或难治性 PCNSL 患者,迫切需要新的治疗方案。


Tirabrutinib 分子结构式

Tirabrutinib 由小野制药发现和开发,这是一种高度选择性、口服布鲁顿酪氨酸激酶 (BTK) 抑制剂,在日本开发用于 B 细胞肿瘤和自身免疫性疾病患者的治疗。B 细胞受体 (BCR) 信号在 B 细胞淋巴细胞的存活、激活、增殖、成熟和分化中发挥着核心作用。BTK 是 BCR 信号通路的重要调节因子,Tirabrutinib 通过抑制 BTK 发挥治疗作用。BTK 是一种胞浆蛋白,在 BCR 受体激活后,受体下游 Lyn、Fyn 等激酶得到激活,进一步激活下游的 BTK 激酶,BTK 激活后调节下游的多条信号。

2014年12月,吉利德与小野制药达成授权协议,获得除日本、韩国、中国、东盟国家 (ASEAN) 以外全球其他国家开发和商业化 Tirabrutinib 的独家权利,小野制药保留上述国家的权利。



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