ADO-Trastuzumab Emtansine

Over the next five years, several blockbuster oncology drugs from leading pharmaceutical companies will lose patent protection, ushering in a wave of patent cliffs that pose significant revenue and strategic risks. This concentrated wave of oncology losses of exclusivity (LOEs) stems from a historic surge in immuno-oncology approvals during the mid-2010s, particularly in checkpoint inhibitors and targeted therapies. Many of these blockbuster assetslaunched between 2014 and 2017were granted expedited pathways, bringing them to market faster but also aligning their exclusivity periods. These cliffs, historically associated with revenue drops that can exceed 50% within two years of LOE, present a critical inflection point, especially for sponsors heavily reliant on a few oncology assets [1].What happens when the cliff hits? The historical signalsHistorical signals from Avastin, Gleevec and Revlimid, illustrate the disruptive nature of such events. Each saw rapid revenue declinesAvastin dropped over 40% post biosimilar entry, Gleevec lost more than 50% of U.S. sales within a year of generic launch, and Revlimid faced a projected 50% erosion despite staggered generic entryunderscoring the urgent need for proactive lifecycle and pipeline strategies [1,2]. Sponsors unprepared for the transition faced valuation declines, market share loss and delayed R&D pivots, either in the reprioritization of promising clinical assets or in investing in registrational-stage ones. Conversely, sponsors with diversified pipelines or aggressive acquisition strategies managed to absorb the impact and maintain momentum. Oncology, due to its high-value therapies and pricing premiums, is particularly vulnerable to erosion once biosimilar and generic competition enters the scene. We took a closer look at the waters ahead to understand how well-positioned companies are to navigate the looming patent cliffs. Drugs like Keytruda, Opdivo and Darzalex approaching LOE represent tens of billions in annual revenue at risk. While some companies have fortified pipelines or pursued lifecycle management strategies, others remain overexposed or delayed in their planning. This snapshot aims to highlight strategic posture as of today, while recognizing that these positions are dynamicand that sponsors still have time to improve their trajectories.Oncology LOE risk and readiness lensTo better understand which companies are strategically positioned to weather the impact of oncology patent cliffs, we developed a readiness framework that assesses both impact exposure and pipeline momentum. The framework incorporates two metrics:An Impact Absorption Score, which evaluates how dependent a company is on a soon-to-expire drug and whether it maintains a broader commercial presence in oncology; and A Clinical Launch Momentum Score, which measures the strength of a company's near-term clinical oncology portfolio, especially the number of late-stage assets with a high likelihood of approval.To complement these, we included a Revenue at Risk metricreflected in the bubble size on the accompanying chartcapturing the absolute dollar value of oncology revenue exposed to LOE. This provides an at-a-glance sense of the potential financial magnitude each company must contend with as they approach key cliff events.Permission granted by Intelligencia AIFrom our perspective at Intelligencia AIthrough access to a comprehensive clinical trial database and regular analysis of the competitive positioning of pharma pipelinesthe current snapshot of patent cliffexposed companies comes as little surprise. We've seen early signals across trial activity, pipeline robustness, and business development behavior. For instance, weve observed that sponsors with consistently high trial initiation rates in post-LOE indications, coupled with targeted in-licensing of late-stage assets, tend to rank higher in readinesspatterns we've seen reflected in companies like Merck Sharp & Dohme (MSD). At the same time, companies with fewer late-stage trials and limited BD&L activity in oncology subtypes where exclusivity is expiring may face a more challenging transition unless strategic adjustments are made. By continuously integrating clinical data in real time with deal flow analytics, sponsors can improve situational awareness and act well before cliff-side impacts become visible in earnings.Our analysis, represented in the graph above, highlights both existing strengths and areas where renewed focus may be required. Some companies already show strong signs of preparation, while others have the opportunity to enhance their resilience through targeted action.Facing the cliff: Whos ready to leap, and whos looking down? To bring this framework to life, we highlight three illustrative sponsorseach occupying a distinct quadrant:Genentech (Roche): Safe harborsPositioned in the upper right quadrant, Genentech combines strong momentum with the ability to absorb impactmaking it a clear example of a Safe Harbor. Despite facing near-term LOEs for Kadcyla and Perjeta, Genentech retains exclusivity for more than fifteen oncology therapies. Notably, almost half of its pipeline has progressed to late-stage development, supporting future revenue continuity. Its relatively balanced revenue distribution across assets limits vulnerability, reducing the size of its Revenue at Risk bubble despite upcoming expiries. Astellas: Storm frontIn the lower left quadrant, Astellas exemplifies the Storm Frontlow absorption capacity paired with limited momentum. With Xtandi approaching LOE and few other oncology products or late-stage candidates to offset the loss, Astellas faces concentrated risk with little in the near-term pipeline to relieve pressure. Its Revenue at Risk is moderate in absolute terms but highly concentrated, amplifying its strategic vulnerability. The window for action remains open, but its narrowing.MSD: Rising tidesMSD is a classic example of a Rising Tidea company with strong clinical momentum but high exposure to a single anchor product. With Keytruda accounting for nearly half of its oncology revenue, MSD carries one of the largest Revenue at Risk profiles in the landscape. However, the company has taken deliberate steps to accelerate its pipeline, with multiple late-stage assets progressing toward approval. This momentum signals a clear effort to offset future erosion and positions MSD to ride the tide of clinical progress, even as it faces a sharp LOE drop from a heavily concentrated revenue base. From Analysis to actionable strategy: Staying ahead of the oncology patent cliffThe oncology patent cliff presents a complex and urgent challenge. As blockbuster therapies approach loss of exclusivity, the consequences for unprepared sponsors can be steepranging from sharp revenue erosion to delayed R&D pivots and weakened market positions. But while the risks are significant, the window for action remains open.Companies best positioned to weather the cliff are those that actively invest in late-stage pipelines, accelerate clinical execution, and pursue external innovation with a sense of urgency. This challenge touches all parts of the organization. Portfolio strategy leaders must reassess timelines and resource allocations with LOE pressure in mind. Search & evaluation teams are racing to identify high-fit external assets amid fierce competition. And BD&L professionals must act decisively to close value-driving deals before the window narrows.This current snapshot reflects where companies stand today, not where they ultimately need to be. Strategic posture in this environment is inherently dynamic. Companies can still shift course by reprioritizing clinical assets, tightening portfolio governance, identifying whitespace for in-licensing, and building partnerships that close therapeutic or modality gaps. Success will hinge on the ability to translate pipeline and market foresight into coordinated, data-driven action.At Intelligencia AI, we equip sponsors to do exactly that drive smarter decisions with the right data, insights and AI. Our solution brings together predictive analytics, clinical data in real-time, and business development intelligence to help teams evaluate risk precisely, monitor competitive activity continuously, and uncover strategic opportunities earlybefore cliff-side impacts appear in earnings.The patent cliff is real and fast approachingbut its outcome is not yet written. For those willing to act decisively, there is still time not only to mitigate the fallout but to emerge stronger, more focused, and better positioned for the next era of oncology innovation.ReferencesKim, M. S., Haslam, A., & Prasad, V. (2025). Trend of sales revenue by year for top-selling cancer drugs in the US and the effect of loss of market exclusivity. Journal of Cancer Policy, 43, 100533. https://doi-org.libproxy1.nus.edu.sg/10.1016/j.jcpo.2024.100533FirstWord Pharma. (2021, April 21). Roche confirms outlook despite drug sales falling 14% in Q1. Retrieved from https://firstwordpharma.com/story/5279321 '

点击蓝字 关注我们 本 期 看 点 由国际肺癌研究协会（IASLC）主办的2025年世界肺癌大会（WCLC）将于当地时间9月6日-9日在西班牙巴塞罗那举行。WCLC是致力于肺癌和其他胸部恶性肿瘤的多学科肿瘤学会议，每届都有来自全球的众多专家学者参会，共同探讨肺癌和其他胸部恶性肿瘤的前沿诊疗进展。 本文就正大天晴在研的Her2 双抗ADC (TQB2102)的最新进展进行汇总。 本期内容 01 TQB2102肺癌进展 02 TQB2102乳腺癌进展 03 其他在研Her2 双抗ADC进展 04 总结与展望 【01 TQB2102肺癌进展】 2025WCLC进展 2025年8 月 13 日，WCLC 2025常规摘要正文发布。正大天晴在大会上首次公布了 HER2 双抗 ADC 产品 TQB2102 治疗非小细胞肺癌（NSCLC）的 II 期临床研究数据。 来源：WCLC 官网 TQB2102 TQB2102是一款靶向HER2蛋白ECD2及ECD4双非重叠表位的双抗ADC药物，其抗体部分通过双表位结合增强了对肿瘤细胞的亲和力与内化效率，同时搭载的拓扑异构酶I抑制剂通过溶酶体酶切释放，精准诱导DNA损伤和细胞死亡。相较于传统单抗ADC，TQB2102的双靶点协同作用显著降低了肿瘤逃逸和耐药风险，临床前研究更显示其对T-DM1耐药细胞株仍具有强效抑制作用。 Cited by：Biotech前瞻 自制幻灯 上表对比了国内外主要HER2靶向产品的机制、适应症和关键临床数据。正大天晴的Her2双抗ADC TQB2102进度靠前。 02 TQB2102乳腺癌进展 突破性疗法认定 2025年7月7日，CDE网站显示，正大天晴的注射用TQB2102拟纳入突破性疗法，用于HER2阳性早期或局部晚期乳腺癌患者的新辅助治疗。 来源：CDE 官网 正大天晴在CDE药物临床试验登记与信息公示平台登记了TQB2102的一项III期临床试验（CTR20251922），该研究将直接对比罗氏经典HER2 ADC药物恩美曲妥珠单抗（T-DM1），评估其在既往接受过抗HER2单抗和紫杉类药物治疗的HER2阳性不可切除局部晚期或转移性乳腺癌患者中的疗效与安全性。这也是TQB2102继HER2低表达乳腺后启动的第二项三期临床。标志着这款全球领跑的双抗ADC药物在乳腺癌治疗领域再迈关键一步。 在2025年ASCO上，TQB2102得到了充分展示。 TQB2102在晚期实体瘤患者中的安全性和有效性探索的首次人体I期临床研究初步数据入选了本次大会口头报告；研究者为中山大学肿瘤防治中心的徐瑞华院长、王树森教授；摘要号为#3003。 主要研究结果整理如下： 截至2024年10月1日，共纳入181例经治无标准治疗方案的晚期实体瘤患者，包括HER2阳性和HER2低表达。 有效性： 6mg/kg及以上剂量组中，HER2阳性乳腺癌ORR为51.3%，HER2低表达乳腺癌ORR为51.5%，HER2 高表达（HER2 免疫组化3+）结直肠癌ORR为34.8%，HER2阳性胃或胃食管结合部腺癌ORR为70%。其中，HER2阳性乳腺癌伴脑转移亚组ORR为70%，1例颅内病灶完全缓解；31%的乳腺癌受试者在T-DM1/DS-8201耐药后使用TQB2102治疗仍有效。 安全性： 总人群中≥3级不良事件主要为中性粒细胞减少（21.7%）、白细胞计数降低 (10.6%)、贫血 (8.9%)、血小板计数降低 (6.1%)等；关于特别关注的ILD，仅出现1例2级ILD（0.55%），发生率远低于同类药物。 上述数据验证了双表位HER2 ADC在伴有HER2表达晚期恶性肿瘤以及伴有脑转移治疗中的有效性和安全性，本研究支持选择6/7.5mg/kg Q3W为扩展阶段推荐剂量。 除了本项研究以外，TQB2102在本次ASCO大会上还公布了2项研究的初步结果。 TQB2102新辅助治疗在局部晚期或早期HER2阳性乳腺癌女性患者中的有效性和安全性：一项随机、开放标签、II期临床试验，入选了本次大会的壁报；通讯作者为复旦大学附属肿瘤医院邵志敏教授；摘要号为#591。 TQB2102在HER2低表达复发或转移性乳腺癌患者中的初步疗效与安全性：一项1b期临床研究结果，入选了本次大会的壁报；通讯作者为 中山大学肿瘤防治中心王树森教授，哈尔滨医科大学附属肿瘤医院张清媛教授；摘要编号为#1090。 之所以如此受到关注程度，也源于双抗ADC是时下火热的赛道，而基于成熟靶点Her2的双抗ADC，相较于Her2 单抗、Her2 ADC，必然要具有更好的疗效和安全性，且全球目前尚未有Her2 双抗ADC的上市，对于TQB2102的初步研究结果，必然引起热议。 【03 其他在研Her2 双抗ADC进展】 Her2(人表皮生长因子受体2)是重要的癌症驱动基因，在多个癌种当中高度表达，其中肺癌检出率约2.5%，乳腺癌检出率约15%~25%，胃癌检出率约20%，胆管癌检出率约20%，卵巢癌检出率约27%，子宫内膜癌中检出率可以达到18%~80%。 很多企业在差异化布局Her2 ADC和Her2 双抗，详情见： FDA批准HER2双抗BTC适应症，老靶点突破胃癌、乳腺癌限制 Her2 ADC丨恒瑞、映恩纳入优先审评，德曲妥珠单抗新增适应症 目前HER2双抗ADC的核心候选药物包括ZW49（Zymeworks/百济神州）、JSKN003（康宁杰瑞）和TQB2102，主要集中在乳腺癌、胃癌、卵巢癌等适应症。尽管尚未获批，其在克服耐药性和治疗泛HER2表达肿瘤中展现出潜力。未来需关注优化后的临床数据和联合疗法的探索。 04 总结与展望 作为中国创新药的代表，TQB2102的首次人体研究数据将于2025年美国临床肿瘤学会（ASCO）年会以口头报告形式全球首发，全面披露其在晚期实体瘤中的疗效与安全。这一高规格亮相不仅彰显国际学术界对中国原研药的认可，更为后续全球化布局奠定基础。 ★