Brentuximab Vedotin

Takeda UK has announced that the National Institute for Health and Care Excellence (NICE) has recommended Adcetris (brentuximab vedotin) as part of a combination treatment for adults with untreated Hodgkin lymphoma (HL). The health technology assessment agency has recommended in final draft guidance that Adcetris be used on the NHS alongside doxorubicin, vinblastine and dacarbazine (AVD) to treat patients with untreated stage 3 or 4 CD30-positive HL. The decision makes Adcetris the first drug to be recommended specifically for previously untreated late-stage classical HL and follows an “improved confidential discount” on the treatment’s list price offered by Takeda, NICE said. HL is a relatively aggressive cancer that occurs when white blood cells called lymphocytes grow out of control. Approximately 2,100 cases are diagnosed in the UK every year, and around 800 people are diagnosed with stage 3 or 4 disease. Adcetris belongs to a class of drugs called antibody-drug conjugates, which combine the selectivity of antibodies with the potent cell-killing power of chemotherapy or other anti-cancer agents. Given as an infusion into a vein, Adcetris specifically targets human CD30-positive tumour cells and will be available immediately through the Cancer Drugs Fund. NICE’s recommendation of the drug was supported by positive results from the late-stage ECHELON-1 trial, which compared Adcetris plus AVD to doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD) in more than 1,300 adults with untreated stage 3 or 4 HL. The study met its primary endpoints, with Adcetris plus AVD demonstrating a statistically significant improvement in modified progression-free survival compared to ABVD. The trial also achieved its key secondary endpoint of overall survival, and the tolerability profile observed with the combination was generally manageable. Emma Roffe, oncology country head, Takeda UK & Ireland said: “[Adcetris] is a medicine that continues to transform the treatment paradigm for patients with HL. We are committed to working in partnership with the clinical and patient community, NICE and the NHS, to ensure as many eligible patients as possible can gain access to this medicine. “We are delighted that NICE recognised the benefit this regimen may bring to patients newly diagnosed with this aggressive disease.” Takeda is responsible for Adcetris’ commercialisation everywhere except in the US and Canada, where Pfizer holds commercialisation rights.

依旧爆火的ADC市场在ADC药物Kadcyla®、Adcetris®取得初步成功后，后续ADC管线的表现可谓是“一波三折”！有的终止临床、强制退市，有的（Enhertu® 和 Trodelvy®，在乳腺癌的治疗中均表现优异）成为明星药物、候选重磅炸弹！真是个，有人辞官归故里，有人星夜赶考场！但是有惊无险，时至今日，ADC药物领域的活动越来越频繁。技术层面已经进行了3个代次的迭代，临床试验有近300项，而管线和公司的BD/并购更是成了医药新闻头条的家常便饭。在BD端，从艾伯维以101亿美元收购ImmunoGen到2023年辉瑞以430亿美元收购Seagen，重磅交易一直是没有中断！ADC药物的交易范围从早期产品到后期再到上市产品，并且包括了各种肿瘤靶点和适应症。首付款总价高达$250B，总的交易额度更是高达$366B!扒开ADC的前世今生自杂交瘤技术出现（1975年）以来，ADC药物的研究就同步拉开帷幕。最初的体外研究与放射性同位素或细胞毒药物偶联的抗体来靶向癌细胞，但低DAR（药物抗体比）、不稳定的Linker和药代动力学太差等问题阻碍了ADC药物早期开发的进展。1983年，ADC（抗癌胚抗原抗体和长春地辛）的首次人体试验被认为在8名晚期转移性癌患者中安全有效。2000年，FDA批准第一个ADC药物：吉妥珠单抗奥佐米星（Mylotarg），不过这个药物后续被退市，捯饬半天后又再次上市。随后，2011年Adcetris，2013年Kadcyla和2017年Besponsa被批准，此阶段ADC药物发展的速度只能说是中规中矩。从2019年以来，获批的ADC数量增加了一倍多，2019至2020年间批准了5个。截止目前，FDA已经批准15款ADC药物上市！除上市ADC药物外，截至目前约有500个左右的ADC药物处于临床试验的不同阶段。这些药物除了在开发抗肿瘤的适应症外，还把ADC的适应症拓展到了非肿瘤领域(如，抗炎、抗感染、神经保护等）靶点知多少“靶点”是很有价值的药物知识点！最开始，ADC的靶点是肿瘤通用HER2和EGFR。最新ADC的研究集中在靶向肿瘤特异性的靶点，从而提高治疗特异性，最大限度地减少毒性问题。另外，研究人员正在探索靶向肿瘤微环境的成分，如基质细胞或脉管系统，以破坏肿瘤生长和转移。下表的靶点，无论是立项、ADC项目评估还是ADC公司评估，都值得深入的学习和分析。短期内，ADC的玩家们，不会跑出这个范围！肿瘤相关的糖蛋白，如粘蛋白和糖化蛋白，由于其在肿瘤中的特异性表达模式也受到关注。下一代的ADC，也有人考虑靶向多种细胞膜受体和蛋白质，从而实现不同的抗肿瘤甚至治疗自免疾病等非肿瘤疾病的可能。ADC单一疗法可能不足以产生足够的抗肿瘤效果，因此对联合疗法的兴趣越来越大。联合治疗通常可降低耐药的可能性，并且可以使用两种具有不同作用机制的药物来获得良好的治疗结果。ADC与化疗、分子靶向药物、放疗、免疫疗法和内分泌疗法的联合治疗正在临床前和临床研究中探索。每年启动的ADC临床试验中约有一半是联合试验（2023年333项ADC 试验中有166项联合治疗）。到2024上半年，共注册了816项ADC联合试验，其中大多数将ADC与免疫检查点抑制剂配对。ADC药物，也可能是PD-1药物延续辉煌的下一个“解药”！目前，有四种ADC药物的联合疗法已获得全球监管机构的批准。END▲点击图片了解  《聚焦“国之大者”CBIITA 联合体荣获“中国产学研合作十大好平台”》更多优质内容，欢迎关注 媒体合作投稿转载/资料领取/加入社群 请添加药小咖与/智/者/同/行   为/创/新/赋/能