Asandeutertinib

On March 9, Synlogic announced that its self-developed drug TY-9591 has successfully outperformed AstraZeneca's renowned lung cancer treatment, Osimertinib, in a pivotal Phase II clinical trial. Founded in 2017, Synlogic is an innovative pharmaceutical company set to go public on the Hong Kong Stock Exchange in August 2024. TY-9591, a deuterated variant of Osimertinib, is the company's lead pipeline candidate. Market reaction to this announcement was swift, interpreting it as a significant challenge to Osimertinib, which is widely regarded as a "miracle drug" for lung cancer. On March 10, Synlogic's stock surged by over 40% in early trading, ultimately closing with a 16.18% increase. In response to this emerging competitor, AstraZeneca stated on March 11 that it could not provide feedback due to the limited information currently available from the study. Osimertinib, the world's first third-generation EGFR-TKI drug, was approved in the U.S. in 2015 and entered the Chinese market in 2017. It has consistently generated robust sales, reaching nearly $5.8 billion globally in 2023. Even with the arrival of domestic third-generation EGFR-TKI drugs, Osimertinib has maintained a dominant position, controlling around 80% of the small molecule targeted lung cancer drug market in China. Notably, Osimertinib's compound patent will not expire until 2032. Synlogic's strategy involves deuterated modifications to Osimertinib. This approach is considered one of the least risky and most straightforward methods to enhance existing drugs. Domestic companies like Zai Lab and HEC Group have also focused on deuterated drugs, with Zai Lab's Donafenib being a notable example that was approved in 2021. In terms of indications, Synlogic is targeting lung cancer with brain metastases, a critical factor affecting the survival of lung cancer patients. The occurrence of brain metastases is significantly higher in patients with EGFR mutations, with risks ranging from 40% to 60%. Osimertinib is recognized for its effectiveness in managing brain metastases, contributing to its success in head-to-head trials. While Synlogic has not disclosed specific Phase II data, it reported that the trial enrolled 224 patients, achieving the primary endpoint of intracranial objective response rate (iORR). More detailed results are expected to be shared at upcoming international or domestic clinical conferences. The announcement has sparked both enthusiasm and skepticism within the industry. Critics have raised questions about Synlogic's choice of objective response rate as the primary endpoint, arguing that it does not align with industry standards and differs from AstraZeneca's original trial design. In a previous instance in September 2024, another company, Kangfang Biopharma, claimed a decisive victory in a head-to-head trial against Merck's Keytruda based on multiple data points, but lacked overall survival data, prompting a cautious response from Merck. Osimertinib's rise to first-line treatment status was largely due to its achievement of significant median progression-free survival (PFS) data. For patients with brain metastases, Osimertinib demonstrated a PFS increase from 9.6 months to 15.2 months, solidifying its reputation as a leading treatment. Although Synlogic has reported an impressive 100% iORR in its single-agent treatment for non-small cell lung cancer with brain metastases, this single data point alone may not be sufficient to sway the medical community, and consensus will depend on comprehensive results. In the competitive landscape, Osimertinib faces challenges not only from Synlogic but also from several other third-generation EGFR-TKI drugs that have recently entered the market. Companies like Betta Pharmaceuticals and Bayer are already exploring fourth-generation TKIs, and Johnson & Johnson's dual-antibody combination has received FDA approval. As Osimertinib stands firm against this growing competition, it is clear that strong clinical data is just one aspect of maintaining its market position. This is a critical factor that Synlogic and other competitors must take into account. On March 11, Synlogic's stock declined nearly 9%, resulting in a market capitalization decrease of over HKD 1 billion.

2017年，阿斯利康的奥希替尼横空出世，凭借对EGFR-T790M耐药突变的精准打击，迅速登顶“肺癌神药”之位，2024年全球销售金额突破65亿美元。然而，八年后，一家名为同源康的中国药企竟用一纸临床数据给它来了个“王座大翻盘”。 2025年3月9日，同源康医药-B（02410）发布重磅公告，其自主研发的第三代EGFR抑制剂TY-9591（商品名：卡达沙®）在对比奥希替尼（商品名：泰瑞沙®）作为一线治疗EGFR突变肺癌脑转移的关键II期临床试验中，脑转移患者的颅内客观缓解率（iORR）显著优于奥希替尼，且在统计学和临床意义上均表现出重大优势。 这场对决已经超越了“谁比谁疗效好”那么简单，它更像是一场“隐形的技术冷战”：当跨国药企还在靠专利红利吃老本，中国药企已经拿着放大镜在分子层面精雕细琢，甚至直接开了个后门，偷偷绕进了奥希替尼的领地。 奥希替尼的中年危机： 不止是专利悬崖，还有天降劲敌 奥希替尼之所以能确立霸权地位，靠的是两个核心支点：一是精准打击T790M突变，让耐药患者“二次重生”；二是超强的血脑屏障穿透力，使其成为“脑转移克星”。然而，没有谁能永远稳坐钓鱼台，奥希替尼正面临三重围攻： 第一重，竞品围攻，奥希替尼腹背受敌。国产第三代EGFR-TKIs竞争激烈，6款国产药已上市，奥赛康利厄替尼加速冲刺，仿制药大军也严阵以待。贝达、豪森、艾力斯等多家企业蓄势待发，低价竞争箭在弦上，奥希替尼市场压力陡增。 第二重，疗效瓶颈，脑转移患者依然“运气成分”占主导。 尽管奥希替尼被称为“脑转移终结者”，但其在脑转移患者中的客观缓解率（iORR）大致为60%-66%，意味着每五个患者中，可能有一个未能从治疗中获益。 第三重，副作用“悄咪咪”成隐形炸弹。 根据2024年WCLC报告的Ⅲ期LAURA研究，奥希替尼治疗不可切除Ⅲ期EGFR突变NSCLC患者时，3级及以上间质性肺炎（ILD）发生率为1.4%（2/143），其中1例为3级，1例为5级（＜1%）。尽管发生率较低，但考虑到对呼吸系统的潜在风险，医生可能会在使用时更加谨慎。 简而言之，奥希替尼正面临着一些挑战，进入了“中年期的调整期”。新技术的崛起给其带来了竞争压力，仿制药的涌现也逐渐蚕食市场份额，而它本身的一些副作用问题可能在一定程度上影响了医生的使用选择。总体来看，奥希替尼正处在一个需要重新审视和适应的关键阶段。 TY-9591 如何在临床数据上“碾压”奥希替尼？ 那么，TY-9591究竟用了什么魔法，让奥希替尼面临如此大的压力？ 答案是——氘代技术，简单来说，就是在分子结构里偷天换日，把特定的氢原子换成氘原子。这个操作看似是“化学家的手滑”，其实藏着三重杀招。 首先是药物的“续航升级”。氘-碳键比氢-碳键更稳定，延长了TY-9591的半衰期，血药浓度持续时间增加30%。翻译成人话：同样的剂量，打怪更久，续航更猛。 其次是毒性减少，剂量“生长”。毒性代谢物AZ5104减少50%，让日剂量从80mg飙升到160mg。想象一下，这是给跑车换上了高功率引擎，速度翻倍的同时，油耗还降低了。 最后是脑部“无视防御”，直穿血脑屏障。让TY-9591的脑脊液浓度达到奥希替尼的3倍以上，脑脊液/血浆浓度比从1.2倍提升到1.8倍，药物穿透力大幅提升。 这波操作直接在临床数据上炸出王炸：在29例可评估脑转移患者中，25例患者达到颅内PR（部分缓解）及4例患者达到颅内CR（完全缓解），颅内客观缓解率iORR为100%。直接把奥希替尼的颅内缓解率和完全缓解率按在地上摩擦。更狠的是，脑转移患者的中位无进展生存期长达17.5个月。 不仅是国内挑战者， TY-9591如何抢滩全球市场？ 全球每年新增约8万例EGFR突变脑转移患者，而欧美市场尚无针对性疗法。TY-9591凭借100%的iORR数据，正站在一个绝佳的跳板上。它不仅可能在国内市场掀起风暴，还可能绕过传统的新药开发路径，跳过I期临床，直接开启国际多中心试验，复制传奇生物CAR-T疗法的出海路线，直面全球竞争。 结束语 奥希替尼曾是EGFR-TKI领域的标志性存在，凭借精准靶向和卓越的血脑屏障穿透力，称霸市场八年。然而，医药行业从来不乏“后来者居上”的故事，TY-9591用氘代技术撕开了一道裂缝，证明了创新并不总是从0到1，把1做到100，同样能改写格局。 真正的竞争，未必是谁取代谁，而是行业整体如何向前。未来，胜出的不会是某个单一药物，而是那些不断进化的企业。毕竟，在抗癌这场马拉松里，唯有变化才是永恒的主题。 免责声明： 文章内容仅供参考，不构成投资建议。投资者据此操作，风险自担, 关于对文中陈述、观点判断保持中立，不对所包含内容的准确性、可靠性或完整性提供任何明示或暗示的保证。请读者仅作参考，并请自行承担全部。 联系我们 SIT 2025 展位火热预定中！ 扫码立即咨询 电话：13816031174 （同微信） 赞助形式包括但不仅限于演讲席位、会场展位、会刊彩页、晚宴赞助、会议用品宣传等。 点击此处“阅读全文”咨询更多精彩！