机构：天风证券 研究员：杨松/曹文清 事件 CSF-1R 高选择性小分子匹米替尼获批上市，用于治疗手术切除可能会导致功能受限或出现较严重并发 症的症状性成人腱鞘巨细胞瘤（TGCT）患者。 EGFR 突变是NSCLC 中最常见的驱动基因突变。尽管第三代EGFR-TKIs 已成为EGFR 突变晚期NSCLC 的一线标准治疗方案，但既往研究提示，对于EGFR突变合并PD-L1 高表达的患者，第三代EGFR-TKIs 的疗效劣于PD-L1 低表达或阴性患者，在PD-L1<50%和PD-L1≥50%的患者中，奥希替尼组的mPFS分别 为23.6 个月和10.2 个月。此外，PD-（L）1 抗体与EGFR-TKI 的联合方案因严重毒副反应而受到限制。 在度伐利尤单抗联合奥希替尼一线治疗EGFRmu NSCLC 的Ib 期临床中，治疗相关毒性反应显著，82% 的患者出现3 级及以上不良事件，其中ILD 发 生率高达38%。 ABSK043 联合伏美替尼的II 期临床数据显示，在21 例EGFR 突变且PD-L1阳性的经治晚期NSCLC 患者 （17 例患者接受过第三代EGFR-TKIs 治疗）中，DCR 达到71%，ORR ...

| 突破性治疗申请公示详细信息 | | | | | --- | --- | --- | --- | | 受理号 CXHL2300625 | | 药品名称 | 甲磺酸伏美替尼片 | | 药品类型 化药 | | 注册分类 | 2.4 | | 申请日期 2025-11-18 | | 承か日期 | 2023-06-08 | | 公示日期 2025-12-25 | | 公示截止日期 | 2026-01-04 | | 是否为罕见病药 台 物 | | | | | 拟定适应症 (或 功能主治) 线治疗。 | | 本品适用于具有表皮生长因子受体 (EGFR) PACC突变的同部晚期或转移性非小细胞肺癌 (NSCLC)成人患者的一 | | | 理由及依据 | 三个文件的公告》(2020年第82号),同意纳入突破治疗药物程序。 | 经审核,本申请符合《药品注册管理办法》和《国家药监局关于发布《突破性治疗药物审评工作程序(试行) 〉等 | | 截图来源：CDE 官网 伏美替尼是第三代 EGFR-TKI，此前已在国内获批两项适应症，用于 EGFR 突变的局部晚期或转移性 NSCLC 成人患者的二线、 一线治疗。今年 7 月，伏美替尼的 ...

Investment Rating - The report maintains an "Outperform" rating for the industry [2]. Core Insights - The third-generation EGFR TKI has become the first-line standard therapy for advanced EGFR mutation NSCLC, significantly extending median progression-free survival (mPFS) to 18.9-22.1 months compared to earlier generations [4][24]. - The domestic EGFR TKI market is expected to exceed 20 billion CNY in 2024, with third-generation EGFR TKIs accounting for 88% of the market share [4][30]. - There is an urgent need to address resistance mechanisms following third-generation EGFR TKI treatment, with ongoing exploration of fourth-generation TKIs, bispecific antibodies, and antibody-drug conjugates (ADCs) [5][32]. Summary by Sections 1. High Incidence of Lung Cancer in China - Lung cancer is the most common malignant tumor globally, with approximately 2.6 million new cases expected in 2024, including about 1.15 million in China [8]. - Non-small cell lung cancer (NSCLC) accounts for around 85% of lung cancer cases, with adenocarcinoma and squamous cell carcinoma being the most prevalent subtypes [8]. 2. Third-Generation EGFR TKI as First-Line Therapy - The third-generation EGFR TKI has established itself as the first-line treatment for advanced EGFR mutation NSCLC, with significant improvements in mPFS compared to first and second generations [4][16][24]. - The report highlights the efficacy of third-generation TKIs in overcoming common mutations and their favorable safety profile [4][24]. 3. Exploration of Resistance Mechanisms - The report discusses the complexity of resistance mechanisms to third-generation EGFR TKIs, including both EGFR-dependent and independent pathways [5][32]. - Current research focuses on developing fourth-generation TKIs targeting specific mutations and exploring combination therapies with bispecific antibodies and ADCs [5][32][39]. 4. Investment Recommendations - The report emphasizes the growth potential of third-generation EGFR TKIs and suggests monitoring companies like Hansoh Pharma and Eli Lilly for market penetration and sales growth [51]. - It also highlights the progress of ADCs and bispecific antibodies in clinical trials, indicating a robust pipeline for future treatments [51][52].

Core Insights - A paradigm shift in cancer treatment is underway, driven by combination therapies rather than single-agent treatments, as highlighted by Pfizer's strategy to focus on ADC combinations instead of direct comparisons with standard treatments or placebos [1][20] - Combination therapies are emerging as a significant trend in innovative drug development, addressing the limitations of single-agent therapies, such as low response rates and inevitable resistance [1][2] Group 1: Advantages of Combination Therapies - Combination therapies enhance efficacy and response rates, delay the onset of resistance, and maintain durable anti-tumor activity, significantly improving clinical value [2][3] - A notable example is the combination of Osimertinib with chemotherapy, which significantly extended the overall survival (OS) of patients with EGFR-mutant advanced non-small cell lung cancer (NSCLC) [2] Group 2: Market Dynamics and Competitive Landscape - The pharmaceutical industry is experiencing a "combination competition" era, where various combination strategies are being employed across different disease areas, leading to synergistic effects [7][20] - AstraZeneca's Osimertinib, despite being a top-selling drug, faces challenges from competitors and is implementing a comprehensive combination strategy to maintain its market position [5][6] Group 3: Ongoing Research and Development - Numerous clinical trials are underway exploring various combination therapies, including PD-(L)1 inhibitors with chemotherapy and other agents, indicating a robust pipeline in the oncology sector [14][19] - The exploration of combination therapies is not limited to solid tumors; significant advancements are also being made in hematological malignancies, showcasing the broad applicability of this approach [10][12] Group 4: Future Directions - The current landscape of drug development suggests that combination therapies will reshape the research and commercial ecosystem of the pharmaceutical industry, emphasizing the need for companies to adapt to this trend to remain competitive [20]

Core Viewpoint - Drug resistance remains the most severe challenge in targeted therapy for lung cancer, with cuproptosis showing promise in overcoming this resistance, although its potential in targeted treatment has yet to be fully explored [1]. Group 1: Research Findings - A study published by researchers from the Chinese Academy of Medical Sciences indicates that inducing cuproptosis enhances the sensitivity of lung cancer to the targeted drug osimertinib and overcomes drug resistance [2][3]. - The research team observed a high degree of synergistic effect between CuET (copper death induction) and osimertinib, indicating that cuproptosis induction increases the anticancer efficacy of osimertinib [5]. - In a secondary screening, cuproptosis was identified as a major vulnerability in osimertinib-resistant cell lines, with the key driver factor FDX1 significantly upregulated in these resistant cells [6]. Group 2: Mechanism of Action - The study highlights that the activation of bypass pathways, particularly involving AKT phosphorylation, is the most common mechanism of drug resistance, accounting for approximately 46% of cases [7]. - Induction of cuproptosis in combination with osimertinib significantly reduced p-AKT levels while increasing the expression of cuproptosis markers and apoptosis markers, suggesting a mechanism for overcoming drug resistance [7]. - In patient-derived organoid models, the combination of CuET and osimertinib outperformed single-agent treatments, demonstrating the potential for enhanced therapeutic efficacy [8]. Group 3: Clinical Implications - The findings suggest that targeting cuproptosis could be a promising strategy to overcome osimertinib resistance, linking it to the commonly overlooked AKT activation mechanism [10]. - With the development of copper ion carriers and nanoparticle delivery systems being actively pursued, these discoveries provide a pathway for clinical translation, necessitating prospective trials to evaluate safety and efficacy [10].

Investment Rating - The report does not explicitly state an investment rating for the pharmaceutical industry Core Insights - The pharmaceutical industry is gradually stabilizing, with a total revenue of 16,766.9 billion yuan in the first three quarters of 2025, reflecting a slight decline of 0.7% year-on-year. The net profit attributable to shareholders decreased by 1.1% to 1,427.5 billion yuan, while the net profit excluding non-recurring items fell by 8.5% to 1,219.9 billion yuan [3][13][37] - Among the 388 selected pharmaceutical companies, 197 companies achieved revenue growth, accounting for 51%, while 189 companies reported positive net profit growth, representing 49% [3][13] - The third quarter of 2025 saw a positive revenue growth rate of 1.9% year-on-year, with net profit showing stable growth [14] Summary by Sections Overall Industry Performance - The pharmaceutical industry experienced a revenue decline of 0.7% in the first three quarters of 2025, with a total revenue of 16,766.9 billion yuan. The net profit attributable to shareholders decreased by 1.1% to 1,427.5 billion yuan [3][37] - The first three quarters showed a quarterly revenue of 5,586 billion yuan in Q1, 5,593 billion yuan in Q2, and 5,588 billion yuan in Q3, with Q3 marking a return to positive growth [14][16] Sector Performance - **Innovative Drugs and Formulations**: Revenue of 3,437.8 billion yuan (+0.6%) and net profit of 342.8 billion yuan (+5.0%) [4] - **Medical Devices**: Revenue of 1,457 billion yuan (-2.4%) and net profit of 265 billion yuan (-14.4%) [5] - **CXO**: Revenue of 695.7 billion yuan (+13.0%) and net profit of 165.4 billion yuan (+60.0%) [5][30] - **Active Pharmaceutical Ingredients**: Revenue of 782.1 billion yuan (-1.5%) and net profit of 114.2 billion yuan (+6.6%) [5] - **Life Sciences Upstream**: Revenue of 60.2 billion yuan (+0.1%) and net profit of 4.4 billion yuan (+15.6%) [5] - **Medical Services**: Revenue of 436 billion yuan (+0.4%) and net profit of 57.3 billion yuan (-13.8%) [5] - **Blood Products**: Revenue of approximately 176 billion yuan (+0.5%) and net profit of approximately 37.7 billion yuan (-20.0%) [5] - **Retail Pharmacies**: Revenue of 859 billion yuan (+0.7%) and net profit of 35.2 billion yuan (+8.9%) [6] - **Pharmaceutical Distribution**: Revenue of 6,087.3 billion yuan (+1.4%) and net profit of 116.8 billion yuan (+5.5%) [6] - **Traditional Chinese Medicine**: Revenue of 2,506 billion yuan (-3.6%) and net profit of 292.7 billion yuan (-0.5%) [6] - **Vaccine Sector**: Revenue of 174 billion yuan (-49.2%) and net profit of -9 billion yuan (-121.6%) [6] Profitability Analysis - The overall industry saw a decline in gross profit margin and net profit margin, with the gross profit margin at 33.7% and net profit margin at 8.5% [37][40] - The CXO sector exhibited the highest growth in net profit, increasing by 60% [31][35] - The medical device sector faced significant profit pressure, with a net profit decline of 14.4% [5][30]

Core Points - Sichuan Huiyu Pharmaceutical Co., Ltd. announced that its wholly-owned subsidiary, Sichuan Huiyu Haiyue Pharmaceutical Technology Co., Ltd., received the acceptance notice from the National Medical Products Administration for the clinical trial application of HYP-6589 tablets, which are intended for use in combination with Osimertinib for treating advanced non-small cell lung cancer with target-driven gene positivity [2] Group 1 - The clinical trial application for HYP-6589 tablets has been accepted, indicating progress in the drug development process [2] - The project research code for HYP-6589 is "HY-0006," highlighting its identification within the company's pipeline [2] - The announcement emphasizes the lengthy drug development cycle and multiple approval stages, which may be influenced by various uncertainties [2]

Core Viewpoint - HYP-6589 tablets, developed by Huayu Pharmaceutical's subsidiary, have received approval for clinical trials in combination with Osimertinib for treating advanced non-small cell lung cancer with target-driven gene positivity, marking a significant step in the company's oncology pipeline [1] Company Summary - Huayu Pharmaceutical's wholly-owned subsidiary, Sichuan Huayu Haiyue Pharmaceutical Technology Co., Ltd., received the acceptance notice from the National Medical Products Administration on November 21 for the clinical trial application of HYP-6589 tablets [1] - The clinical trial aims to explore the combination treatment of HYP-6589 with Osimertinib for advanced non-small cell lung cancer, a significant indication in oncology [1] - As of the announcement date, there are no similar products approved for market release in both domestic and international markets, indicating a potential first-mover advantage for the company [1] Industry Summary - The approval for clinical trials of HYP-6589 in combination with Osimertinib highlights the ongoing innovation and development in the oncology sector, particularly for targeted therapies in lung cancer treatment [1] - The absence of competing products in the same category suggests a growing opportunity for companies focusing on advanced treatments for non-small cell lung cancer [1]

Core Viewpoint - Huiyu Pharmaceutical (688553) announced that its wholly-owned subsidiary, Huiyu Haiyue, received a notice of acceptance from the National Medical Products Administration for the clinical trial application of HYP-6589 tablets in combination with Osimertinib for the treatment of advanced non-small cell lung cancer with target-driven gene positivity, marking a significant step in the development of this innovative drug [1] Company Summary - Huiyu Pharmaceutical's HYP-6589 is classified as a Category 1 innovative chemical drug, indicating its novel nature in the pharmaceutical market [1] - There are currently no similar products approved for sale domestically or internationally, highlighting the potential market opportunity for HYP-6589 [1]

Core Insights - HYP-6589, a selective SOS1 small molecule inhibitor developed by the company's subsidiary, has received acceptance for clinical trial application in combination with Osimertinib for treating advanced non-small cell lung cancer with target-driven gene positivity [1][2] - The drug is classified as a Class 1 innovative chemical drug and is currently undergoing clinical research for monotherapy in advanced solid tumors in China [1] - There are no similar products approved for market in both domestic and international markets as of the announcement date [1] Group 1 - HYP-6589 has received the acceptance notice from the National Medical Products Administration for clinical trials [1] - The drug is designed to enhance the efficacy of Osimertinib and potentially overcome resistance mechanisms associated with it [2] - Preclinical studies indicate that the combination of SOS1 inhibitors and Osimertinib can achieve deeper and more sustained inhibition of MAPK and PI3K signaling pathways [2] Group 2 - SOS1 is a crucial regulator in the RTK-RAS signaling pathway, which is activated by receptor tyrosine kinases [2] - The activation of SOS1 leads to the formation of RAS-GTP, which is essential for downstream signaling pathways [2] - Inhibition of SOS1 has shown potential to address unmet clinical needs in the context of Osimertinib resistance [2]