Carboplatin

GlobalData market analysts predict that Elahere could generate up to $1.98bn in revenue for AbbVie by 2030. Credit: Skorzewiak via Shutterstock. The European Commission (EC) has granted marketing authorisation to AbbVie ’s Elahere (mirvetuximab soravtansine) for the treatment of folate receptor-alpha (FRα) platinum-resistant ovarian cancer, a decade since the approval of the latest treatment. Antibody-drug conjugate (ADC) Elahere has received European approval for the treatment of adult patients with FRα positive, platinum-resistant high-grade serous epithelial ovarian, fallopian tube or primary peritoneal cancers. The therapy is authorised for patients who have undergone one to three prior systemic treatment regimens. Approximately 35%-40% of ovarian cancer patients express FRα, a biomarker specifically targeted by Elahere. By delivering the cytotoxic agent DM4 directly to cancer cells while sparing healthy tissue, the treatment aims to minimise off-target effects and reduce toxicity compared to traditional chemotherapy. Elahere’s approval is supported by data from the Phase III MIRASOL trial (NCT04209855), which enrolled 453 patients with FRα-positive platinum-resistant ovarian cancer. The treatment demonstrated a significant and clinically meaningful 35% reduction in the risk of disease progression or death, compared to standard chemotherapy. Patients treated with Elahere had a median progression-free survival (PFS) of 5.6 months, slightly longer than the four months observed in patients who received standard chemotherapy. Moreover, patients in the Elahere arm showed a median overall survival (OS) of 16.5 months while those in the investigator’s choice chemotherapy arm had a median OS of 12.8 months. The approval of Elahere addresses an unmet need for patients with platinum-resistant ovarian cancer. “It’s been ten years since a new treatment for platinum-resistant ovarian cancer was approved in the EU, and now oncologists have an effective, new, targeted treatment option for these patients,” said Toon Van Gorp, professor of gynaecological oncology at the University of Leuven. AbbVie inherited Elahere as part of a $10.1bn acquisition of ImmunoGen . The drug received accelerated approval by the US Food and Drug Administration (FDA) in November 2022 and was granted full FDA approval in the US in March 2024. GlobalData market analysts predict that Elahere could generate up to $1.98bn in revenue for AbbVie by 2030. As the first FRα-targeted ADC approved in the EU, Elahere represents a competitive advantage for AbbVie in the ovarian cancer treatment landscape. GlobalData is the parent company of Pharmaceutical Technology. Elahere faces competition from Bristol Myers Squibb and Eisai ’s ADC farletuzumab ecteribulin, which is currently being investigated in Phase II trials. However, Elahere holds the first-to-market advantage. The drug is currently being investigated in three other ovarian cancer trials, in combination with Roche’s Avastin (bevacizumab) in the Phase III GLORIOSA study (NCT05445778), as a monotherapy in the Phase II PICCOLO study (NCT05041257), and with carboplatin in another Phase II trial (NCT05456685).

2024年9月，康方生物在2024世界肺癌大会上发布依沃西单药（PD-1/VEGF双特异性抗体）对比默沙东帕博利珠单抗单药一线治疗PD-L1表达阳性（PD-L1 TPS≥1%）的局部晚期或转移性非小细胞肺癌（NSCLC）的注册性Ⅲ期临床研究(HARMONi-2/AK112-303）的重磅研究数据。 两个月后，默沙东也买了一款PD-1/VEGF双特异性抗体：LM-299。 除了默沙东，还有多家大药企都已押注PD-(L)1双抗。该领域近两年交易不断，其中中国Biotech是主要的转让方。 表1 国产PD-(L)1/VEGF药物授权出海记录 资料来源：根据公开资料整理 >01< PD-1单抗危机 免疫疗法（Immuno-oncology, IO）作为癌症治疗的突破，旨在增强机体的自然防御能力从而消除恶性肿瘤细胞。 肿瘤免疫治疗的策略包括免疫检查点抑制剂、细胞因子治疗、癌症疫苗、溶瘤病毒疗法和过继细胞疗法等五大类别。 其中以PD-1单抗为代表的免疫检查点抑制剂(Immune Checkpoint Inhibitor, ICI)最为成功，竞争也最为激烈。 在全球市场，默沙东的PD-1单抗Keytruda（帕博利珠单抗，K药）在2023年销售额达到250亿美元，成功登顶药王宝座。今年K药继续攻城略地，在三阴乳腺癌（TNBC）、肾细胞癌（RCC）和非小细胞肺癌（NSCLC）等肿瘤早期适应症上进一步渗透，今年前三季度K药销售额已达216亿美元。 但是“药王”的危机已经显现。 今年9月，康方生物在2024世界肺癌大会（WCLC）上宣布其PD-1/VEGF双特异性抗体依沃西头对头挑战K药成功。 据康方新闻稿，依沃西HARMONi-2研究是全球首个对比帕博利珠单抗取得显著阳性结果的随机、双盲、对照Ⅲ期临床研究。数据显示，依沃西一线治疗PD-L1阳性NSCLC，相比帕博利珠单抗显著延长了患者的中位无进展生存期（mPFS），具有统计学和临床双重显著性。K药组的mPFS是5.82个月，这一数据已在多项研究中得到验证；而依沃西单抗组的mPFS高达11.14个月，HR值是0.51，意味着依沃西单抗为患者降低了49%的疾病进展或死亡的风险。 此外，依沃西单抗安全性数据同样可圈可点，并未引入新的安全隐患。 HARMONi-2研究结果堪称“惊艳”，无疑给默沙东带来了不少压力。 2024年11月14日，默沙东宣布，已协议获得礼新医药新型在研PD-1/VEGF双特异性抗体LM-299的全球开发、生产和商业化独家许可。根据协议条款，礼新医药将获得5.88亿美元的首付款。基于LM-299多项适应证的技术转让、开发、获批和商业化进展，礼新医药还将获得最高27亿美元的里程碑付款。 LM-299与康方生物的依沃西单抗同为PD-1/VEGF双特异性抗体，可见默沙东也对“肿瘤免疫+抗血管生成”抗肿瘤双机制的认可。 >02< PD-(L)1双抗或将接棒？ PD-1和VEGF常在实体瘤中表达上调和共表达，抗 VEGF 药物在促肿瘤血管正常化和刺激 免疫激活方面与免疫检查点抑制剂（ICI）具备协同作用。 与抗VEGF单药或 PD-(L)1 单药相比，PD-(L)1/VEGF 双抗上的单个抗体臂可通过独特的协同机制增强药物分子另一端抗体臂与对应靶点的结合活性，从而更有效地 阻断与配体的相互作用和下游信号传导作用。 图片来源：国联证券 康方生物在HARMONi-2研究的大获成功，证明了PD-(L)1/VEGF双抗有迭代PD-1单抗的潜力。 目前，依沃西单抗已在国内获批上市，联合培美曲塞和卡铂用于治疗经表皮生长因子受体（EGFR）酪氨酸激酶抑制剂（TKI）治疗后进展的EGFR基因突变阳性的局部晚期或转移性非鳞状NSCLC患者。依沃西用于PD-L1 阳性（TPS≥1%）NSCLC 患者一线治疗也已提交上市申请。 其他处于临床阶段的PD-(L)1/VEGF管线也几乎都来自中国，因此引发了国产PD-(L)1/VEGF药物授权出海热潮。 表2 临床阶段在研PD-(L)1/VEGF 双抗 数据来源：药智数据 除PD-(L)1/VEGF 双抗，PD1/CTLA4双抗、PD1/4-1BB双抗，PD-1/IL-2融合蛋白、PD1/IL15融合蛋白等PD-(L)1双靶点药物相继对K药发起了挑战。 图片来源：国联证券 >03< 结  语 人类肿瘤药物治疗史上经历了从化疗药物到靶向药物、免疫治疗药物的迭代创新，使肿瘤患者的生存状况得到了极大的改善，也因此诞生了K药、O药两款年销售额超百亿美元的PD-1单抗。 但PD-1单抗仍然面临低响应率、安全性和耐药性等问题，因此开发新一代免疫疗法深受市场期待。目前来看，PD-1/VEGF双抗率先拿下一局，期待该领域的更多惊喜。 参考资料： 1. 默沙东中国：默沙东协议获得礼新医药在研PD-1/VEGF双特异性抗体LM-299全球独家许可 2. 康方生物Akeso：全球首个对比帕博利珠单抗取得显著阳性结果的随机对照大III期研究——依沃西HARMONi-2重磅研究成果在WCLC发表 3. 国联证券：PD-(L)1 双靶点药物再掀免疫治疗热潮（一） 声明：本内容仅用作医药行业信息传播，为作者独立观点，不代表药智网立场。如需转载，请务必注明文章作者和来源。对本文有异议或投诉，请联系maxuelian@yaozh.com。 责任编辑 | 史蒂文 转载开白 | 马老师 18996384680（同微信） 商务合作 | 王存星 19922864877（同微信）  阅读原文，是受欢迎的文章哦