A Randomised, Phase II Trial to Evaluate the Efficacy of Ivonescimab, a PD 1/VEGF Bispecific Antibody, Versus FOLFOX as Second Line Therapy for Locally Advanced/Metastatic Biliary Cancers

The object of this trial is to test whether ivonescimab is superior to standard chemotherapy (FOLFOX regimen) for the treatment of patients with advanced biliary tract cancer after failure of a first line of chemotherapy. It is only open to patients who participated in the SAFIR-ABC10 trial (NCT05615818) but did not receive experimental treatment.
Eligible patients will be randomised (2:1) to receive either ivonescimab or FOLFOX. Treatment will be continued until disease progression, or a maximum of 34 cycles of ivonescimab (experimental arm), whichever occurs first.

开始日期2025-01-30

申办/合作机构

UNICANCER

[+2]

NCT06601335 / Not yet recruiting临床3期

A Randomized, Controlled, Multicenter Phase 3 Study of AK112 in Combination with AK117 Versus Pembrolizumab As First Line Treatment for a Programmed Cell Death-ligand 1 (PD-L1) Positive Population with Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma (R/M HNSCC)

This is a phase 3 study. All subjects arerecurrent or metastatic head and neck squamous Cell Carcinoma (R/M HNSCC), Eastern Cooperative Oncology Group (ECOG) performance status 0-1. The purpose of this study is to evaluate the efficacy and safety of AK112 combined with AK117 versus pembrolizumab combined with placebo in patients with R/M HNSCC whose tumors have programmed cell death-ligand 1 (PD-L1) positive [Combined Positive Score (CPS) greater than or equal to 1].

开始日期2024-10-01

申办/合作机构

中山康方生物医药有限公司

100 项与依沃西单抗相关的临床结果

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100 项与依沃西单抗相关的转化医学

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100 项与依沃西单抗相关的专利（医药）

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项与依沃西单抗相关的文献（医药）

2024-12-31·mAbs

Antibodies to watch in 2024

Article

作者: Reichert, Janice M ; Kaplon, Hélène ; Crescioli, Silvia ; Wang, Lin ; Visweswaraiah, Jyothsna ; Chenoweth, Alicia

The 'Antibodies to Watch' article series provides an annual summary of commercially sponsored monoclonal antibody therapeutics currently in late-stage clinical development, regulatory review, and those recently granted a first approval in any country. In this installment, we discuss key details for 16 antibody therapeutics granted a first approval in 2023, as of November 17 (lecanemab (Leqembi), rozanolixizumab (RYSTIGGO), pozelimab (VEOPOZ), mirikizumab (Omvoh), talquetamab (Talvey), elranatamab (Elrexfio), epcoritamab (EPKINLY), glofitamab (COLUMVI), retifanlimab (Zynyz), concizumab (Alhemo), lebrikizumab (EBGLYSS), tafolecimab (SINTBILO), narlumosbart (Jinlitai), zuberitamab (Enrexib), adebrelimab (Arelili), and divozilimab (Ivlizi)). We briefly review 26 product candidates for which marketing applications are under consideration in at least one country or region, and 23 investigational antibody therapeutics that are forecast to enter regulatory review by the end of 2024 based on company disclosures. These nearly 50 product candidates include numerous innovative bispecific antibodies, such as odronextamab, ivonescimab, linvoseltamab, zenocutuzumab, and erfonrilimab, and antibody-drug conjugates, such as trastuzumab botidotin, patritumab deruxtecan, datopotamab deruxtecan, and MRG002, as well as a mixture of two immunocytokines (bifikafusp alfa and onfekafusp alfa). We also discuss clinical phase transition and overall approval success rates for antibody therapeutics, which are crucial to the biopharmaceutical industry because these rates inform decisions about resource allocation. Our analyses indicate that these molecules have approval success rates in the range of 14-32%, with higher rates associated with antibodies developed for non-cancer indications. Overall, our data suggest that antibody therapeutic development efforts by the biopharmaceutical industry are robust and increasingly successful.

2024-09-01·Med

EGFR-mutated NSCLC: A roadmap to treatment sequences

Review

作者: Girard, Nicolas

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are the standard of care for the management of EGFR-mutated non-small cell lung cancer. Recent results from the HARMONi-A trial lead to considering ivonescimab-a first-in-class, bispecific antibody targeting PD-1 and VEGF-plus chemotherapy as a new second-line option following third-generation TKIs.

2024-08-20·JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION

Ivonescimab Plus Chemotherapy in Non–Small Cell Lung Cancer With EGFR Variant

Article

作者: Zhang, Yu ; He, Zhiyong ; Li, Wenting ; Jia, Yuming ; Xia, Michelle ; Liang, Wenhua ; Zhou, Ningning ; Du, Xiaobo ; Huang, Jianan ; Liu, Chunling ; Wang, Zhiyu ; Yang, Hui ; Yang, Lei ; Fan, Yun ; Yang, Kunning ; Luo, Yongzhong ; Song, Qibing ; Xu, Shen ; Liu, Baogang ; Chen, Yuan ; Li, Mingjun ; Zhang, Zhihong ; Lu, Dongmei ; Jia, Li ; Lv, Dongqing ; He, Ming ; Fang, Wenfeng ; Feng, Jifeng ; Zhao, Hongyun ; Guo, Jun ; Liu, Xianling ; Li, Xiaoling ; Hu, Mingxiu ; Zhao, Yuanyuan ; Wang, Yan ; Liu, Laiyu ; Feng, Weineng ; Li, Wei ; Wang, Zhongmin Maxwell ; Wu, Di ; Cheng, Ying ; Huang, Yan ; Hu, Ying ; Yang, Runxiang ; Guo, Yubiao ; Peng, Jiewen ; Lan, Haitao ; Wang, Yongsheng ; Chen, Hualin ; Dong, Xiaorong ; Su, Haichuan ; Zhou, Jianya ; Chen, Likun ; Li, Wen ; Lu, Hong ; Li, Baiyong ; Zhou, Ming ; Zhang, Li ; Chen, Yongxing ; Lu, Junguo ; Hou, Xue ; Yi, Tienan ; Li, Kai ; Zhao, Hui ; Sun, Yulan ; Li, Mengxia ; Xu, Fei ; Wang, Zhen ; Song, Xia

Importance:

For patients with non–small cell lung cancer whose disease progressed while receiving EGFR tyrosine kinase inhibitor (EGFR-TKI) therapy, particularly third-generation TKIs, optimal treatment options remain limited.

Objective:

To compare the efficacy of ivonescimab plus chemotherapy with chemotherapy alone for patients with relapsed advanced or metastatic non–small cell lung cancer with the epidermal growth factor receptor (EGFR) variant.

Design, Setting, and Participants:

Double-blind, placebo-controlled, randomized, phase 3 trial at 55 sites in China enrolled participants from January 2022 to November 2022; a total of 322 eligible patients were enrolled.

Interventions:

Participants received ivonescimab (n = 161) or placebo (n = 161) plus pemetrexed and carboplatin once every 3 weeks for 4 cycles, followed by maintenance therapy of ivonescimab plus pemetrexed or placebo plus pemetrexed.

Main Outcomes and Measures:

The primary end point was progression-free survival in the intention-to-treat population assessed by an independent radiographic review committee (IRRC) per Response Evaluation Criteria in Solid Tumors version 1.1. The results of the first planned interim analysis are reported.

Results:

Among 322 enrolled patients in the ivonescimab and placebo groups, the median age was 59.6 vs 59.4 years and 52.2% vs 50.9% of patients were female. As of March 10, 2023, median follow-up time was 7.89 months. Median progression-free survival was 7.1 (95% CI, 5.9-8.7) months in the ivonescimab group vs 4.8 (95% CI, 4.2-5.6) months for placebo (difference, 2.3 months; hazard ratio [HR], 0.46 [95% CI, 0.34-0.62]; P &lt; .001). The prespecified subgroup analysis showed progression-free survival benefit favoring patients receiving ivonescimab over placebo across almost all subgroups, including patients whose disease progressed while receiving third-generation EGFR-TKI therapy (HR, 0.48 [95% CI 0.35-0.66]) and those with brain metastases (HR, 0.40 [95% CI, 0.22-0.73]). The objective response rate was 50.6% (95% CI, 42.6%-58.6%) with ivonescimab and 35.4% (95% CI, 28.0%-43.3%) with placebo (difference, 15.6% [95% CI, 5.3%-26.0%]; P = .006). The median overall survival data were not mature; at data cutoff, 69 patients (21.4%) had died. Grade 3 or higher treatment-emergent adverse events occurred in 99 patients (61.5%) in the ivonescimab group vs 79 patients (49.1%) in the placebo group, the most common of which were chemotherapy-related. Grade 3 or higher immune-related adverse events occurred in 10 patients (6.2%) in the ivonescimab group vs 4 (2.5%) in the placebo group. Grade 3 or higher vascular endothelial growth factor–related adverse events occurred in 5 patients (3.1%) in the ivonescimab group vs 4 (2.5%) in the placebo group.

Conclusions:

Ivonescimab plus chemotherapy significantly improved progression-free survival with tolerable safety profile in TKI-treated non–small cell lung cancer.

Trial Registration:

ClinicalTrials.gov Identifier: NCT05184712

707

项与依沃西单抗相关的新闻（医药）

2024-09-20

·药智网

股价一周大涨50%，3年创新高，这家Biotech仍被低估？

近日，康方生物股价大涨约50%，3年后终破新高。在全球股市的风暴之下，作为港股全年唯3涨幅大于50%的生物医药公司（截至2024年9月17日同花顺问财数据），康方生物能够逆势捅破新高，原因几何？从一项临床研究结果谈起。近期，康方生物在2024世界肺癌大会上发布了公司自主研发的全球首创PD-1/VEGF双特异性抗体新药依沃西单药对比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（中国市场的临床多中心研究）。数据显示，依沃西单抗在与帕博利珠单抗的头对头试验取得胜利，依沃西单抗成为全球首个且唯一在单药头对头III期临床研究中证明疗效显著优于帕博利珠单抗的药物。简单来说，康方生物依沃西单抗在“药王”K药最核心、最赚钱的肺癌领域正面硬刚且击败了K药，股价应声上涨，实属正常。但是，作为“新王”候选者，康方生物的地位似乎还没有受到国内市场足够的重视，在华福证券给予“买入”评级目标价81.89港元的情况下，康方生物在9月19日早市仍大跌11%收约64港元，不禁引人深思。有望突破300亿， K药跑马圈地进行时每一个药王的崛起似乎都有迹可循：无药可敌的疗效、广泛的适应症、极速扩张的市场营销策略。默沙东K药（帕博利珠单抗）从2014年上市以来，便以一骑绝尘之姿横扫世界肿瘤药物市场，销售额年复合增长率高达51%（以2016-2023年计算），最终在2023年以250亿美元销售额击败蝉联10年“药王”桂冠的修美乐（144亿美元），夺下全球“药王”宝座。并且据默沙东财报，K药第二季度销售额达到73亿美元，同比增长21%，2024Q1环比增长5.8%。至此，K药在2024年上半年的全球销售额达到142亿美元，全年销售额有望突破300亿美元，药王二连冠已然收入囊中。图1 2022Q2-2024Q2年K药销售情况图片来源：默沙东年报 2014年6月，由百时美施贵宝和日本小野公司共同开发的纳武单抗(Opdivo，也称O药)，是PD-1抑制剂里面的“First in class”，率先在日本上市。同年9月，K药在美国通过FDA认证，批准上市。虽然，K药并不是第一个PD-1获批药物，但却是第一个把跑马圈地应用到极致的PD-1治疗药物。 PD-1市场之争，关键在于获批的适应症的深度与广度。面对O药的先发优势，K药的竞争策略很简单即后发先至，就一个字“快”。图2 2015—2024年K药和O药适应症获批情况统计数据来源：O药和K药在FDA当年最后一份补充文件，笔者手动统计在K药快速跑马圈地的策略下，FDA获批适应症数量，2018年起已经快速反超O药，而且两者之间的差距持续拉大。不仅如此，在获批深度适应症中，K药更是在非小细胞癌（NSCLC）一线治疗领域的天王山之战当中击败了O药。图3 Keynote-024（K药）VS Checkmate-026（O药）一线治疗非小细胞癌（NSCLC）临床试验结果对比图片来源：新浪医药至此，K药凭借快速扩张适应症与非小细胞癌（NSCLC）一线治疗领域的胜利，完成了对O药的弯道超车，销售额碾压，最终成就了自己的药王之位。按照现有增速，预计在28年核心专利到期之前，K药年销售额有望突破500亿美元，但此想法在依沃西单抗打败K药后，似乎过于乐观。大涨50%，康方生物仍被低估？当领地无法扩张，市场进入存量，Me too是下下策，Best in class才是唯一解。 PD-1药物即将度过跑马圈地的时期，对于后来者追击速度已然不及，想要分一杯羹，只有从药效的硬核打击着手。要知道，虽然药王K药目前已经占据了大量的适应症，但在2028年药王核心专利过期后，市场上将会出现雨后春笋般的大量Me too仿制药铺满这些药王曾经占据的领地。为什么说中国股市还是低估了康方生物硬刚K药的利好，就是由于康方生物的依沃西单抗预判到了未来的红海前景，选择成为挑战者而非跟随者。康方生物的依沃西单抗选择在K药的大本营NSCLC正面硬刚，可谓是走了一步好棋。不仅避开了专利到期后与Me too药物的低价厮杀，还选择了一块最肥美的市场作为逐渐蚕食药王的发力点。溃败往往是从核心据点开始的。在肿瘤领域，得肺癌者得天下。肺癌，是K药的大本营。正如K药凭借NSCLC一线治疗领域的胜利逆袭O药的故事，康方生物似乎将让历史重演。因此，一只名不见经传的美股已经选择了用手投票。在上周的美股市场里公开数据显示，一只名为Summit Therapeutics(SMMT.US)的股票异军突起，一周爆拉160%，全年涨幅更是达到惊人的1123.37%，登上美国热搜。为什么Summit这么牛？我们来看一则公告，2022年12月6日，康方生物与Summit Therapeutics Inc.订立合作及许可协议，康方生物将授予Summit于美国、加拿大、欧洲及日本开发及商业化其突破性双特异性抗体依沃西(PD-1/VEGF，AK112)的独家许可权。可以看出，美国市场的投资者对于依沃西单抗挑战并超越药王的市场前景非常看好。而康方生物的未来也很明确，按照适应症的优先度一项一项地进行快速挑战。一般来说，‌中国获批创新药从批准开展临床试验至获准上市所用时间平均为7.2年。值得注意的是，据康方生物2024年半年财报显示，通过单药和联合用药，依沃西已针对肺癌、胰腺癌、乳腺癌、肝细胞癌结直肠癌等17个瘤种开展了25+项临床试验，且有三项Ⅲ期临床研究启动。但这样的速度相较于2028年这个可预见的红海市场，似乎仍不够敏捷（2018年，国内市场上只有2个企业分庭抗礼，至2023年已经初步形成4大头部+一众尾部的竞争格局）。图4 2018—2023年国内上市PD-(L)1靶点创新药企业竞争格局数据来源：药智数据，药智咨询整理猛击药王才是唯一出路表面上短期的销售与研发实力是药企的双擎，但实际上药企面向未来的长期策略才是一个药企变强的关键。内卷、伪创新、跟随而非挑战通常是大多数创新药企的生存策略，短期来看可以让自己避开错误的道路，但是长期来看却也无法拿下药王的桂冠。为什么？第一，现在早已经过了野蛮增长的年代，随着药物种类的发展，适应症无对应药物的情况会越来越少，未来不会缺同质化的药物，缺乏的是更有效的药物，要想不在me too的红海领域里面厮杀，只能通过更优质的药物去赋新现有的市场。第二，国内药物的价格通常只有国外的十分之一，出海势在必行，而出海的必备要素是药物的竞争优势足够大，才能够在国外打开市场。第三，创新药药王往往占据着最大、最富有经济价值的山头，新药想要登基必须击碎旧王的先发优势，时间不站在新药这边，只能从药效着手。所以，对创新药药企而言，敢于横刀立马挑战药王，真正的不负创新二字，才是长期发展的正确策略。对于依沃西单抗能否在中国以外的临床试验数据挑战K药成功，且关注后续国外多中心临床结果公布。参考来源： 1.《209 vs 93：K药销售额碾压O药的原因？》，生物制药进展杂评 2.默沙东财报 3.《一周大涨160%，1款好药足以改命！》，智通财经网 4.《中国新药注册临床试验进展年度报告（2023年）》 5.《逆袭成功！Keytruda销售额第一次超越Opdivo》，新浪医药 6.华福证券 7.同花顺问财声明：本内容为作者独立观点，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 | 斯蒂文转载开白 | 马老师 18996384680（同微信）如需定制医药咨询服务，请扫描下方二维码咨询！阅读原文，是受欢迎的文章哦

财报临床3期上市批准医药出海申请上市

2024-09-20

·BioSpace

ADCs, Bispecifics and Radiopharma Take Center Stage at ESMO24

iStock, CIPhotos The European Society for Medical Oncology’s annual meeting this week featured the hottest emergent areas of cancer treatment—antibody-drug conjugates, bispecifics and radiopharmaceuticals—while anti-TIGIT therapies made a bit of a comeback. The oncology space is riding a high this week. A tsunami of trial data for novel therapies was released at the 2024 European Society for Medical Oncology (ESMO) Congress, held Sept. 13 to 17 in Barcelona, Spain. Meanwhile, in the U.S., the American Association for Cancer Research this week released its annual report, which showed that established treatments are helping people live longer. To that end, Bristol Myers Squibb presented Phase III results at ESMO for its already approved Opdivo-Yervoy combination demonstrating that after 10 years, 43% of patients who received the combo for melanoma were alive with many not needing subsequent therapy. That’s a vast leap for a cancer that just a decade ago was an almost certain death sentence. When it comes to novel therapies, TIGIT made a bit of a comeback at ESMO after a string of failures in the drug class, as GSK and iTeos revealed data for their inhibitor belrestotug—in combination with Jemperli—which elicited promising response rates in patients with non-small cell lung cancer (NSCLC). Still, with higher immune-related toxicity, GlobalData argued that the TIGIT combo “will have to deliver a convincing [overall survival] benefit to switch physicians’ prescribing habits from the existing PD-1 regimens and to build resiliency against emerging first-line threats from pipeline antibody-drug conjugates and bispecific antibodies.” Indeed, bispecifics and antibody-drug conjugates (ADCs) were both on prominent display at ESMO. For ADCs, Jefferies analysts flagged data readouts in ovarian cancer for more than 10 candidates in various clinical stages. Results from the Phase II TROPION-PanTumor03 study showed that AstraZeneca and Daiichi Sankyo’s ADC datopotamab deruxtecan (Dato-DXd) exhibited promising antitumor activity and manageable toxicity in patients with advanced ovarian and endometrial cancer post-platinum chemotherapy. Sutro Biopharma also saw positive antitumor activity in updated data from a Phase Ib study of its ADC Luvelta, in combination with bevacizumab, for patients with epithelial ovarian cancer, with an overall response rate of 35%. And on the biospecifics front, BioNTech made a splash at ESMO when it reported that its PD-L1- and VEGF-A-targeting antibody BNT327 elicited a 57.8% confirmed objective response in a Phase II trial of patients with EGFR-mutant NSCLC. These data follow those from Summit Therapeutics, which impressed at the World Conference on Lung Cancer earlier this month with late-stage data for its bispecific ivonescimab, declaring victory over Merck’s blockbuster Keytruda, which has historically led the NSCLC treatment space. “This [bispecific] therapeutic modality has definitely arrived,” Ryan Schoenfeld, CEO of The Mark Foundation for Cancer Research, told BioSpace this week. Prostate Cancer Radiopharma to ‘Go Nuclear’ There were also significant developments at ESMO in the radiopharmaceuticals space, with Lantheus Holdings presenting data from an analysis of its Phase III SPLASH trial showing that its radioligand therapy PNT2002 significantly improved progression-free survival in PSMA-positive metastatic castration-resistant prostate cancer (mCRPC). However, William Blair analysts were underwhelmed, writing in a note to investors that the new data “did not materially alter” their view of PNT2002, which they see as inferior to Novartis’ Pluvicto. GlobalData forecasted this week that revenue for Pluvicto will jump from $980 million in 2023 to $4.3 billion by the end of the decade, dominating sales of radiopharma options for prostate cancer, which GlobalData predicted will “go nuclear.” Pluvicto, which was approved by the FDA in March 2022, is indicated for mCRPC patients who are positive for the PSMA protein. Novartis is seeking a label expansion to enable physicians to prescribe Pluvicto for patients with mCRPC who have not yet undergone chemotherapy. In addition, Novartis presented data at ESMO showing Pluvicto’s activity in combination with docetaxel in metastatic hormone-sensitive prostate cancer. “It is expected that Pluvicto will be at the forefront of the drug class in terms of market dominance until the turn of the decade, when alternate radiation-emitting ligands can make their mark,” Thomas Wales, oncology and hematology analyst at GlobalData, said in a statement. With worldwide sales of radiopharma drugs for prostate cancer expected to reach $6.3 billion by 2030, according to GlobalData, it’s no wonder that Novartis earlier this month announced it is building a new facility in California—the company’s third U.S.-based radioligand therapy production site—and expanding an Indianapolis site for producing isotopes for cancer treatment. It seems Novartis is making moves to remain king of the red-hot radiopharma space.

临床结果临床3期ASCO会议上市批准临床2期

2024-09-19

·同写意

中国创新药的未来在哪里？

2024医美与器械创新前沿华西论坛，与您共探药企转型之道，解锁消费医疗市场新机遇。10月12日，成都等您来！在中国创新药的悠悠岁月中，Biotech一度在迷雾中徘徊，寻找着那一线生机。如今看来，“出海”布局全球市场，似乎是通往未来的答案。当License out交易井喷，当出海成为新的增长引擎，当越来越多Biotech实现盈利，国内创新药企的日子似乎好了起来。然而，出海之路并非坦途，国产创新药被“退货”的案例比比皆是。这一现象折射出License out交易进入了“深水区”：BD交易“过热”容易导致市场泡沫和资源错配。由此引发了值得深思的问题：中国创新药的未来在哪里？到底该如何出海？什么样的创新药才能实现国际化？ 1 困境与觉醒中国创新药的发展之路，并非一帆风顺。医保控费、资本遇冷、现金流枯竭，尤其是仿创思维、“拿来主义”导致产业过于内卷，中国创新药的问题展露无遗。要知道，每个新药的诞生都伴随着高昂的研发成本与漫长的研发周期。可随着众多药企扎堆于热门靶点，使得同质化竞争严重、市场快速饱和，导致创新药企难以获得理想的回报，面临现金流紧张的困境。面对国内市场空间有限且激烈的竞争环境，众多创新药企如同千军万马过独木桥。由此，布局全球市场成为了必由之路。国产创新药出海的模式包括自主出海、借船出海（License out），其中License out是将自身产品的海外权益或全球权益对外授权许可给外资药企，可获得首付款+里程碑费用+销售分成，现已成为国内Biotech缓解资金压力、加速新药研发的重要途径。近年来，国产创新药License out大手笔频现，交易金额持续攀升：从荣昌生物的纬迪西妥单抗（26亿美元）到康方生物的AK112（50亿美元），再到百利天恒的BL-B01D1（84亿美元），国内创新药出海的纪录一破再破。据医药魔方统计，2023年中国创新药企业通过BD获得的首付款总额达267.64亿元，首次超过IPO渠道募资总额，并且是后者的近两倍。而且，2024年上半年国内药企达成了约42项License out授权合作，累计交易总金额255亿美元，较去年同期增长80%。可见，国内Biotech已经找到了新的出路。毕竟，许多国内创新药企都尝到了依靠BD收入实现盈利的甜头，包括康方生物、和黄医药、亚盛医药、科伦博泰、百利天恒等。 2023年，康方生物实现首次年度盈利，主要得益于产品销售额同比增长48%，以及获得技术授权和技术合作收入约29.23亿元，其中收到Summit就依沃西单抗（AK112，PD-1/VEGF）支付的授权许可首付款5亿美元。 2024年上半年，血液肿瘤领域龙头亚盛医药首次实现盈利，主要来源于产品销售收入和对外合作授权收入，目前已收到武田就耐立克支付的选择权付款7.2亿元和股权投资款项5.4亿元；同期，科伦博泰也实现扭亏，已就多条合作管线收到默沙东总额为9000万美元（约合人民币6.4亿元）的里程碑付款。特别是百利天恒，在收到BMS就EGFR/HER3双抗ADC BL-B01D1支付的8亿美元首付款后，上半年营业收入同比增长超16倍至55.53亿元。一言以蔽之，国内Biotech已经迎来了觉醒时刻。 2 出海即是出路？尽管出海已成为国内创新药企“活下去”的必由之路，但这条路并非只有坦途，也有不少坎坷：国产创新药被退回权益的案例屡见不鲜。这一现象的出现，存在着多重因素：既有市场环境变化的原因，包括竞争者数量增多、外资药企调整战略，也有新药立项时缺乏前瞻性和创新性，未能满足跨国药企对市场潜力的要求，以及新药研发成效不佳，缺乏显著的临床价值。实际上，新药研发本身就是“赌”，License out交易也是一场“赌局”。对于外资药企而言，先支付首付款支持国内创新药企研发新药，之后看新药能否展现出优异的疗效和显著的市场前景，再决定是否继续行使权益、支付金额更高的里程碑付款。反之，国内创新药企在拿到首付款后，不仅能缓解资金压力、继续推进新药研发，后续新药若能顺利研发，就有望拿到更高的里程碑付款以及一定的销售分成，还能借助外资药企打开国际化市场。尽管BD出海不易，仍不乏实现双赢的案例。近年来出现中国创新药撑起美国药企市值的现象，便是有力的证明。例如，Arrivent公司在2021年以“总额8亿美元（其中首付款4000万美元）+一定比例股份”引进艾力斯伏美替尼的海外权益后，不仅完成了两次融资（总金额超3亿美元），还在2024年1月成功登陆美股市场。市场普遍认为，鉴于伏美替尼在国内市场的优异销售表现，艾力斯拿到7.65亿美元的里程碑付款只是时间问题。类似的案例，还有今年成功冲刺美股市场的Alumis。 Alumis于6月上市，IPO规模达2.1亿美元，是今年以来IPO发行规模第三大的Biotech，核心管线是2021年以“6000万美元首付款+1.2亿美元里程碑付款”从海思科引进的TYK2抑制剂ESK001。凭借这款具有同类最佳潜力的药物，Alumis在3年时间累计融资达5.29亿美元（不含IPO融资）。毕竟，TYK2赛道可是成为了香饽饽：BMS的Sotyktu，是全球首款且唯一获批上市的TYK2抑制剂，2023年大卖1.7亿美元，BMS预计其2030年销售额将超过40亿美元；2022年，武田制药以“40亿美元预付款+20亿美元里程碑款”收购了Nimbus的NDI-034858（TAK-279）。最典型的案例，莫过于康方生物和Summit。 2022年底，Summit以总额50亿美元引进康方生物的依沃西单抗在美国、加拿大、欧洲和日本的开发和商业化权益。彼时，Summit的股价仅有1美元左右，与康方生物达成合作后股价在短短几个交易日最高飙升至近6美元。尤其今年5月以来，受依沃西单抗头对头击败K药的亮眼临床数据刺激，Summit股价接连大涨，再加上9月12日宣布获得今年的第二次融资后，当天股价大涨至27.41美元，总市值达近200亿美元。当下的创新药市场，无不希望看到更多类似这样双向奔赴且没有输家的交易。 3 通往未来的答案新型的创新药出海模式NewCo，可谓是海内外药企实现共赢的第二条路。所谓NewCo模式，就是将公司产品管线海外权利授予海外新成立的公司，获得股权及资金支持，同时引入海外基金，搭建国际化团队，实现产品出海。简言之，就是国内创新药企通过技术入股，与海外资本一起攒局。目前，已有不少药企成功借助NewCo模式实现创新药出海，包括艾力斯、恒瑞医药、康诺亚、嘉和生物、岸迈生物。前文所述的艾力斯与ArriVent就伏美替尼达成的海外授权合作，便是“现金+股权”的NewCo模式。今年5月，恒瑞医药将GLP-1类创新药产品组合HRS-7535、HRS9531、HRS-4729在大中华区以外的全球权益授予美国Hercules公司，不仅达成交易总额60亿美元，还将取得Hercules公司19.9%的股权。紧接着7月，康诺亚将2款双抗新药CM512、CM536授予Belenos Biosciences，将获得1.8亿美元交易总额以及Belenos公司30.01%的股权；8月，嘉和生物将CD20/CD3双抗GB261授予TRC 2004，将获得后者数量可观的股权、数千万美元的首付款、高达4.43亿美元的里程碑付款以及销售分成。 NewCo模式的好处在于，国内药企不仅能通过早期管线创造一定价值，又能通过股权，降低自身风险、参与公司决策，并锁定更多远期收益。中国创新药以多种模式频频出海，找到了通往未来的第一个答案。但不同的药企，需根据自身的实际情况灵活决定采用哪种模式。什么样的创新药才能实现国际化？解答这一问题，实际上就是回答中国创新药的未来在哪里？这点从近年来达成的License out交易即可窥见一斑。百利天恒BL-B01D1之所以获得BMS以总额84亿美元（首付款8亿美元）引进，不仅在于源头创新（全球首创且唯一进入临床阶段的HER3xEGFR双抗ADC），而且具有广泛的抗肿瘤活性。据Insight数据库显示，目前BL-B01D1共有7个III期临床正在进行中，包括肺癌、乳腺癌、鼻咽癌、食管鳞癌。此外还有14项II期临床正在进行中，覆盖瘤种超过10个。和黄医药的呋喹替尼能获得武田制药以总额超11亿美元（首付款4亿美元）引进，就在于有扎实的全球多中心临床数据支持，使其能登陆美国市场，且放量速度快于国内市场。呋喹替尼是美国10年来获批的首款且唯一针对三线mCRC的小分子靶向药，并凭借优异疗效被写入NCCN指南。亚盛医药就奥雷巴替尼（耐立克）与武田达成总额13亿美元的授权合作，创下了国产小分子肿瘤药对外BD最高纪录，并获得武田入股，同样在于源头创新思维。耐立克是国内首个且唯一获批上市的第三代BCR-ABL抑制剂，解决了临床空白问题，且疗效和安全性均优于武田的泊那替尼。引进耐立克后，武田便拥有了与诺华的阿思尼布抗衡、巩固CML统治地位的底气。归根结底，唯有具有显著的创新性和临床价值、优异疗效且具有广阔市场前景的创新药，才能实现国际化。而源头创新思维，决定了中国创新药未来的方向。参考文献： 1.各家公司的财报、公告、官微 2.《医药行业创新药出海专题：国际化渐入佳境，洞悉出海潜力管线》，西南证券 3.《创新药出海新模式NewCo：恒瑞、康诺亚、岸迈生物、嘉和生物...》，新康界，2024-09-11 4.平安证券、首创证券研报同写意媒体矩阵，欢迎关注↓↓↓

IPO引进/卖出

100 项与依沃西单抗相关的药物交易

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研发状态

批准上市

10 条最早获批的记录,

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适应症	国家/地区	公司	日期
EGFR阳性非鳞状非小细胞肺癌	中国	康方赛诺医药有限公司	2024-05-21

未上市

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
PD-L1阳性非小细胞肺癌	申请上市	中国	康方赛诺医药有限公司	2024-07-27
PD-L1阳性非小细胞肺癌	申请上市	中国	康方药业有限公司	2024-07-27
复发性头颈部鳞状细胞癌	临床3期	中国	中山康方生物医药有限公司	2024-10-01
晚期胆道癌	临床3期	中国	中山康方生物医药有限公司	2024-08-25
鳞状非小细胞肺癌	临床3期	中国	中山康方生物医药有限公司	2023-08-17
非鳞状非小细胞肺癌	临床3期	中国	中山康方生物医药有限公司	2022-01-25
肝细胞癌	临床3期	-	中山康方生物医药有限公司	-
皮肤鳞状细胞癌	临床2期	美国	Summit Therapeutics, Inc.	2025-02-28
晚期胆管癌	临床2期	比利时	Summit Therapeutics, Inc.	2025-01-30
晚期胆管癌	临床2期	法国	Summit Therapeutics, Inc.	2025-01-30

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临床结果

适应症

分期

评价

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT05227664 (ESMO2024)	临床2期	三阴性乳腺癌一线 PD-L1 combined positive score (CPS)	30	Ivonescimab 20 mg/kg Q2W + Paclitaxel 90 mg/m2	蓋襯觸鹹齋簾範願憲齋(鑰醖繭膚簾獵築鹹艱壓) = 繭壓範壓簾鑰鏇憲製壓獵憲壓膚鏇繭鹽選蓋簾 (鏇醖齋鬱鹽顧醖鬱觸窪 )	积极	2024-09-16
				Ivonescimab 20 mg/kg Q2W + Nab-paclitaxel 100 mg/m2	衊製淵願築艱鑰襯鑰範(廠簾積淵鹹願願餘膚鏇) = 餘選艱壓醖獵壓獵選簾簾願簾窪選壓選淵淵構 (艱艱糧製鏇夢製簾鬱製, 44.3 ~ 83.8)
NCT05229497 (ESMO2024) 人工标引	临床2期	头颈部鳞状细胞癌一线 PD-L1 Positive	30	Ivonescimab monotherapy	鬱簾願製簾醖製壓簾壓(夢觸窪淵鬱構築遞遞艱) = 夢壓築壓獵觸醖鏇範顧鏇憲糧構築願構淵窪繭 (廠膚衊膚襯夢鹽簾憲衊 ) 更多	积极	2024-09-14
				Ivonescimab plus ligufalimab	鬱簾願製簾醖製壓簾壓(夢觸窪淵鬱構築遞遞艱) = 積簾膚齋願範夢壓鑰衊鏇憲糧構築願構淵窪繭 (廠膚衊膚襯夢鹽簾憲衊 ) 更多
NCT05382442 (ESMO2024)	临床2期	转移性结直肠癌一线 \| 维持 KRAS \| BRAF \| MSS	40	FOLFOXIRI + Ivonescimab	鬱選獵鏇獵夢淵鏇鑰繭(選簾鹹製糧範鏇憲範淵) = 衊顧壓鬱網餘鹽夢鹽艱範築築網廠淵鏇齋鹽顧 (鏇鹹餘壓淵鹽夢壓築鏇 ) 更多	积极	2024-09-14
				FOLFOXIRI + Ivonescimab + Ligufalimab	鬱選獵鏇獵夢淵鏇鑰繭(選簾鹹製糧範鏇憲範淵) = 觸膚餘範鹹網衊製壓願範築築網廠淵鏇齋鹽顧 (鏇鹹餘壓淵鹽夢壓築鏇 ) 更多
NCT05247684 (WCLC2024) 人工标引	临床2期	可切除非小细胞肺癌	60	Ivonescimab 20 mg/kg	襯願醖網積鬱糧繭築簾(顧簾構齋築繭夢選淵窪) = The most common TRAEs (incidence ≥5%) of grade 3 or higher were decreased neutrophil count and decreased white blood cell count 鏇鹹選觸淵膚顧願夢顧 (膚醖蓋觸醖鑰醖夢網遞 ) 更多	积极	2024-09-08
				Ivonescimab plus chemotherapy
NCT05499390 (HARMONi-2 \| AK112-303, WCLC2024) 人工标引	临床3期	PD-L1阳性非小细胞肺癌一线 PD-L1 Positive	398	Ivonescimab 20 mg/kg	衊顧觸製膚餘醖艱範夢(願簾糧鹹積製夢構觸糧) = 壓衊餘繭夢夢觸鏇鏇鏇窪繭鑰憲簾壓鏇艱觸選 (襯網壓壓獵襯淵窪襯願 ) 更多	积极	2024-09-08
				Pembrolizumab 200 mg	衊顧觸製膚餘醖艱範夢(願簾糧鹹積製夢構觸糧) = 膚衊鏇鹽齋構網範鹹淵窪繭鑰憲簾壓鏇艱觸選 (襯網壓壓獵襯淵窪襯願 ) 更多
NCT05499390 (AK112-303 \| HARMONi-2, NEWS) 人工标引	临床3期	PD-L1阳性非小细胞肺癌一线 PD-L1 Positive	398	依沃西	壓餘餘構鹽範鹽繭夢膚(網齋構糧選繭顧鹹淵積) = 在意向治疗人群(ITT)中，依沃西组相较于帕博利珠组显著延长了患者无进展生存期（PFS），风险比（HR）显著优于预期簾願壓窪齋壓窪壓憲壓 (鬱衊範醖鏇觸襯鏇簾網 ) 达到	优效	2024-05-31
				帕博利珠
NCT05184712 (Pubmed)	临床3期	EGFR C797S 突变非小细胞肺癌 epidermal growth factor receptor (EGFR) variant	322	Ivonescimab plus pemetrexed and carboplatin	鏇鹹夢遞鏇憲鬱製網壓(願餘糧鏇窪鑰繭鬱選餘) = occurred in 10 patients (6.2%) in the ivonescimab group vs 4 (2.5%) in the placebo group 鹽鬱網鑰艱簾窪選醖選 (憲衊鏇夢遞簾淵艱蓋繭 ) 更多	积极	2024-05-31
				Placebo plus pemetrexed and carboplatin
NCT05184712 (HARMONi-A, ASCO2024) 人工标引	临床3期	EGFR阳性非鳞状非小细胞肺癌 EGFR T790M	322	Ivonescimab + Chemotherapy	鬱鬱願鏇觸廠鑰窪淵遞(襯齋積鬱壓蓋築築膚糧) = 窪顧遞蓋繭壓憲範範餘鑰鏇蓋願觸窪簾憲築衊 (願構襯齋鬱鑰襯衊鑰醖, 5.85 ~ 8.74) 更多	积极	2024-05-24
				Placebo + Chemotherapy	鬱鬱願鏇觸廠鑰窪淵遞(襯齋積鬱壓蓋築築膚糧) = 繭鹹淵鬱餘艱窪顧繭願鑰鏇蓋願觸窪簾憲築衊 (願構襯齋鬱鑰襯衊鑰醖, 4.21 ~ 5.55) 更多
NCT04047290 (Pubmed) 人工标引	临床1期	晚期恶性实体瘤 PD-1 \| VEGF-A	51	Ivonescimab	廠壓構廠窪鏇鏇遞願獵(顧遞糧範壓醖蓋淵齋獵) = 鏇築鹹憲網簾製鬱窪積餘膚艱鏇廠窪蓋構齋齋 (鑰窪壓構獵蓋願蓋淵選 ) 更多	积极	2024-04-19
NCT04736823 \| NCT04900363 (AK112-202, ESMO_ELCC2024) 人工标引	临床1/2期	脑转移瘤 \| 非小细胞肺癌一线	35	ivonescimab+platinum doublet chemotherapy (AK112-201)	鑰構願齋獵遞窪夢鏇憲(衊窪齋壓願築簾積觸廠) = 12 pts (34%) achieved an IC response. Of these, 11 had received PC/ivo, among whom 7 achieved an IC complete response (CR); 1 pt achieved an IC CR among the 7 pts who received ivo alone. 積壓觸獵淵鏇製範襯餘 (鑰窪製齋艱蓋淵醖齋製 ) 更多	积极	2024-03-22
				ivonescimab+platinum doublet chemotherapy (AK112-202)