Larotrectinib Sulfate

再鼎医药瑞普替尼（Augtyro）近期连续迎来重大进展：继2024年5月中国NMPA批准其用于ROS1阳性非小细胞肺癌后，6月又获FDA加速批准用于NTRK融合实体瘤治疗，目前CDE拟将其纳入优先审评。 这款双靶点TKI药物正快速改写国内精准治疗市场版图。 ■ 破局耐药难题的"双靶利器" 作为全球首个同时靶向ROS1/NTRK的新一代TKI，瑞普替尼通过独特的ATP结合口袋抑制机制，有效克服G2032R等常见耐药突变。TRIDENT-1研究数据显示：在TKI初治患者中达到58%客观缓解率（含15%完全缓解），更值得注意的是，对于经治耐药患者仍保持50%缓解率，且对脑转移患者展现显著颅内活性。 ■ 中国市场"抢滩登陆战" 瑞普替尼5月获批即进入国家谈判目录，定价5894元/盒（40mg*120粒）。 尽管面临恩曲替尼、拉罗替尼等竞品压力，但其双靶点优势明显：国内ROS1阳性NSCLC患者约2.3万例，NTRK融合实体瘤年新发约2.5万例，且现有治疗存在显著未满足需求。 ■ 商业化前景多维透视 1. 疗效优势：对比同类药物颅内缓解率提升30%-50% 2. 医保加持：谈判后价格较进口竞品低40%以上 3. 适应症拓展：覆盖12岁以上儿童实体瘤患者 4. 联用潜力：与PD-1抑制剂联用研究已进入II期 据摩熵医药预测，2025年中国市场销售额有望突破5亿元，全球市场或达12亿美元规模。 行业启示 1. 双靶点策略成突破方向：瑞普替尼验证了跨癌种靶点联用的商业价值 2. 真实世界数据积累关键：需持续监测G2032R等耐药突变发生率 3. 渠道布局重点：需强化在肺癌专科医院和儿童肿瘤中心的准入 对于研发企业，该品种的成功提示：在泛瘤种药物开发中，突破性疗效数据+快速适应症扩展+医保准入的组合拳，仍是抢占市场的核心策略。 关于瑞普替尼 瑞普替尼（Repotrectinib）是一种口服酪氨酸激酶抑制剂，靶向ROS1、NTRK和ALK融合基因。其作用机制是通过抑制上述激酶的活性，阻断下游信号通路，从而抑制肿瘤细胞生长和增殖。该药设计为第二代抑制剂，可克服第一代TKI（如克唑替尼、恩曲替尼）治疗后常见的耐药突变（如ROS1 G2032R、NTRK G595R等）。 适应症包括ROS1阳性非小细胞肺癌（NSCLC）和NTRK融合阳性实体瘤（如甲状腺癌、肉瘤等）。临床研究（TRIDENT-1试验）显示，在未接受过TKI治疗的ROS1阳性NSCLC患者中，客观缓解率（ORR）达79%，中位缓解持续时间（DoR）为34.1个月；在既往接受过TKI治疗且存在ROS1耐药突变的患者中，ORR为38%。对于NTRK融合阳性实体瘤患者，ORR为58%。 研发企业为百时美施贵宝（BMS），其前身Turning Point Therapeutics于2022年被BMS收购。瑞普替尼的关键价值在于解决ROS1/NTRK靶向治疗耐药问题，被FDA认定为突破性疗法。2023年11月，FDA加速批准其用于ROS1阳性NSCLC，成为该领域首个覆盖初治和经治患者的二代TKI。 全球市场方面，瑞普替尼2024年第一季度销售额为2400万美元，分析师预测其年销售额峰值可能突破10亿美元。在中国，该药于2023年5月被国家药监局（NMPA）纳入优先审评，适应症为ROS1阳性NSCLC，2024年5月获批上市，并已被纳入医保谈判。 国内竞争药物包括辉瑞的洛普替尼（Lorlatinib）和罗氏的恩曲替尼（Entrectinib），但瑞普替尼在耐药突变覆盖率和缓解持续时间上具有优势。 使用”摩熵药筛“小程序，随时关注产品申报进展。

Eli Lilly said Thursday that its fourth-quarter revenue jumped 45% to $13.53 billion over the prior year, though this fell short of earlier projections. The drugmaker also reiterated the $58 billion to $61 billion in anticipated 2025 revenue it outlined last month. The revenue miss was not a surprise. At the annual JP Morgan Healthcare Conference last month, Lilly anticipated it would fall $400 million below its fourth-quarter revenue estimate as wholesalers bought less of its obesity drug Zepbound than expected. The guidance sent Lilly’s shares down about 7% on Jan. 14. It marked two quarters in a row of lower-than-expected sales for the Indianapolis drug giant. Lilly’s earnings came a day after its obesity and diabetes rival, Novo Nordisk, reported its performance over the past 12 months. The Danish drugmaker disclosed a 26% spike in sales over 2023. Novo anticipates less growth this year, though, at about 16% to 24%. The two obesity competitors are attempting to expand the scope of their current medicines — Zepbound and Wegovy — and get a whole new line of treatments approved as dozens of drug development rivals try to play catch-up in the most lucrative pharmaceutical market. To meet demand and stay ahead of the pack, Lilly and Novo have each spent more than $10 billion buying up, building and revamping manufacturing facilities. Both have also been fending off compounding pharmacies. Lilly also disclosed the culling of four programs, including an unnamed dual amylin and calcitonin receptor agonist for obesity that was in Phase 1. A spokesperson said the program was part of Lilly’s partnership with KeyBioscience . Lilly also removed three Phase 2 programs, including a failed Alzheimer’s drug , an atopic dermatitis candidate known as ucenprubart and an experimental heart failure medicine known as volenrelaxin. Endpoints News reported on the axed heart failure program last week. Meanwhile, the world’s largest pharmaceutical maker (by market cap) said it ramped up R&D spending 18% to $3.02 billion in the fourth quarter. Lilly also took a $344 million asset impairment and restructuring charge in the fourth quarter, compared to $67.7 million in the same period of 2023. The latest charges “primarily included an intangible asset impairment associated with Vitrakvi.” Lilly got the cancer drug via its Loxo Oncology acquisition, and Bayer eventually took the full rights to Vitrakvi. So far this year, Lilly has been busy. It’s made a small cancer biotech acquisition , earned an FDA approval for treating Crohn’s disease and funneled $500 million into a new VC fund . Toward the end of last year, Lilly also said it would spend another $15 billion to repurchase shares after completing a prior $5 billion share buyback program earlier that quarter.