Elironrasib

疾病控制率达94%！KRAS小分子抑制剂获突破性疗法认定Revolution Medicines今日宣布，其RAS（ON）G12C选择性抑制剂elironrasib（RMC-6291）获得美国FDA授予的突破性疗法认定，用于治疗既往接受过化疗和免疫治疗、但未使用过KRAS G12C抑制剂的KRAS G12C突变局部晚期或转移性非小细胞肺癌（NSCLC）成年患者。之前公布的试验结果显示，在36名既往接受免疫疗法和化疗的KRAS G12C突变NSCLC患者中，每日两次200 mg剂量下的elironrasib展现良好的耐受性，药物相关不良事件（TRAEs）主要为低等级。在该剂量下，患者的客观缓解率（ORR）为56%，疾病控制率（DCR）为94%，中位无进展生存期（PFS）为9.9个月。Elironrasib是一款大环分子，其作用机制与分子胶类似，通过将KRAS G12C和cyclophilin A粘合在一起，形成的三元复合体阻断处于激活状态（ON）的KRAS G12C与RAS效应蛋白结合，从而抑制下游信号传导。治疗溃疡性结肠炎，创新小分子达两项关键3期试验主要终点Abivax公司近日公布其口服、潜在“first-in-class” miR-124增强剂obefazimod（ABX464）在两项关键性3期试验ABTECT-1（Study 105）和ABTECT-2（Study 106）中的积极顶线结果。这两项为期8周的研究旨在评估obefazimod治疗中重度活动性溃疡性结肠炎（UC）成人患者的疗效与安全性。试验纳入的患者群体分布均衡，其中47.3%的患者对包含JAK抑制剂在内的既往治疗应答不足。结果显示，每日一次50 mg的obefazimod在两项试验的汇总分析中，安慰剂校正的临床缓解率达到16.4%（p<0.0001），分别在ABTECT-1中达到19.3%（p<0.0001），在ABTECT-2中达到13.4%（p=0.0001），均具有高度统计学意义和临床意义，达成主要终点。此外，obefazimod也达成所有的关键次要终点。该药物的整体耐受性良好，未观察到新的安全性信号。目前，维持治疗研究ABTECT-107正在进行中，预计将于2026年第二季度公布顶线结果。Obefazimod能够通过上调miR-124的表达来抑制许多炎症反应介导物的生产，进而缓解溃疡性结肠炎等炎症疾病。抗体偶联寡核苷酸疗法获FDA突破性疗法认定，年底递交上市申请Avidity Biosciences今日宣布，其用于治疗杜氏肌营养不良（DMD）的在研疗法delpacibart zotadirsen（del-zota）获得美国FDA授予的突破性疗法认定，用于治疗适用于外显子44跳跃治疗的杜氏肌营养不良症（DMD44）患者。该疗法目前正在进行2期EXPLORE44开放标签延伸试验（EXPLORE44-OLE）。Avidity预计将在2025年底按计划向FDA提交生物制品许可申请（BLA）。之前公布的研究结果显示，剂量为5 mg/kg和10 mg/kg的del-zota均表现出强有力的骨骼肌递送能力，骨骼肌中寡核苷酸水平达到200 nM。外显子44跳跃效率显著增加40%。抗肌萎缩蛋白生成显著增加，平均增加至正常水平的25%，最高达到正常水平的58%。肌酸激酶水平下降至接近正常水平，相比基线减少了超过80%。Del-zota由靶向1型转铁蛋白受体（TfR1）的单克隆抗体和促进编码抗肌萎缩蛋白的mRNA前体产生外显子44跳跃的寡核苷酸偶联而成，TfR1在肌肉组织中高度表达。这款疗法通过改变mRNA剪接过程，产生几乎与正常抗肌萎缩蛋白功能相同的蛋白。靶向TfR1的单克隆抗体可以通过与肌肉细胞表面的受体相结合，增强寡核苷酸的肌肉特异性递送。参考资料：[1] Abivax Announces Positive Phase 3 Results from Both ABTECT 8-Week Induction Trials Investigating Obefazimod, its First-in-Class Oral miR-124 Enhancer, in Moderate to Severely Active Ulcerative Colitis. Retrieved July 23, 2025 from https://www.globenewswire.com/news-release/2025/07/22/3119843/0/en/Abivax-Announces-Positive-Phase-3-Results-from-Both-ABTECT-8-Week-Induction-Trials-Investigating-Obefazimod-its-First-in-Class-Oral-miR-124-Enhancer-in-Moderate-to-Severely-Active-.html[2] Avidity Biosciences Receives FDA Breakthrough Therapy Designation for Delpacibart Zotadirsen (del-zota) for the Treatment of DMD in People with Mutations Amenable to Exon 44 Skipping. Retried July 23, 2025 from https://www.prnewswire.com/news-releases/avidity-biosciences-receives-fda-breakthrough-therapy-designation-for-delpacibart-zotadirsen-del-zota-for-the-treatment-of-dmd-in-people-with-mutations-amenable-to-exon-44-skipping-302511334.html[3] Revolution Medicines Announces FDA Breakthrough Therapy Designation for Elironrasib. Retrieved July 23, 2025 from https://www.globenewswire.com/news-release/2025/07/23/3120187/0/en/Revolution-Medicines-Announces-FDA-Breakthrough-Therapy-Designation-for-Elironrasib.html免责声明：本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。版权说明：欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权请在「药明康德」微信公众号回复“转载”，获取转载须知。分享，点赞，在看，聚焦全球生物医药健康创新

Breakthrough Therapy Designation granted to elironrasib for the treatment of adult patients with KRAS G12C-mutated locally advanced or metastatic non-small cell lung cancer who have received prior chemotherapy and immunotherapy but have not been previously treated with a KRAS G12C inhibitor Designation based on encouraging clinical data observed with elironrasib in patients with advanced KRAS G12C non-small cell lung cancer REDWOOD CITY, Calif., July 23, 2025 (GLOBE NEWSWIRE) -- Revolution Medicines, Inc. (Nasdaq: RVMD), a late-stage clinical oncology company developing targeted therapies for patients with RAS-addicted cancers, today announced that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation to elironrasib, the company’s RAS(ON) G12C-selective inhibitor, for the treatment of adult patients with KRAS G12C-mutated locally advanced or metastatic non-small cell lung cancer (NSCLC) who have received prior chemotherapy and immunotherapy but have not been previously treated with a KRAS G12C inhibitor. The Breakthrough Therapy Designation is based on data from the Phase 1 RMC-6291-001 clinical trial evaluating elironrasib monotherapy in patients with advanced KRAS G12C solid tumors. Results from the trial have demonstrated highly competitive antitumor activity, including differentiated safety and tolerability along with a compelling objective response rate and progression-free survival. “There continues to be a need for new targeted therapies for patients with RAS-addicted cancers, and this Breakthrough Therapy Designation from the FDA highlights the therapeutic potential of elironrasib, a differentiated inhibitor, for patients with KRAS G12C lung cancer,” said Mark A. Goldsmith M.D., Ph.D., chief executive officer and chairman of Revolution Medicines. “Coming shortly after daraxonrasib was granted a designation for patients with advanced RAS mutant pancreatic cancer, this designation for elironrasib further validates our innovative product engine as a source for novel potential treatment approaches for patients with RAS mutant cancers.” Elironrasib is an innovative inhibitor that binds selectively and covalently to the oncogenic RAS(ON) form of the RAS G12C variant that drives approximately 12% of cases of NSCLC. Revolution Medicines is exploring elironrasib monotherapy and combinations in various treatment settings and continues work to prioritize multiple options for advancing its development. NSCLC accounts for 80%-85% of all lung cancers, and most patients have advanced or metastatic disease at initial diagnosis.1,2 KRAS mutations are found in nearly 30% of NSCLC cases, among which KRAS G12C is the most common. Currently there are no RAS-targeted inhibitors with full approval by the FDA to treat patients with KRAS G12C NSCLC.3 Breakthrough Therapy Designation is intended to expedite the development and review of potential new medicines designed to treat serious conditions and address significant unmet medical needs. Pursuant to FDA guidelines, the medicine needs to have shown encouraging preliminary clinical evidence that demonstrates substantial improvement on a clinically significant endpoint over available medicines. About Non-Small Cell Lung CancerMore than 197,000 people are diagnosed with non-small cell lung cancer (NSCLC) in the U.S. each year.4 Despite treatment advancements, NSCLC remains a leading cause of cancer-related mortality worldwide, primarily due to its late-stage diagnosis and limited response to conventional therapies. About Revolution Medicines, Inc. Revolution Medicines is a late-stage clinical oncology company developing novel targeted therapies for patients with RAS-addicted cancers. The company’s R&D pipeline comprises RAS(ON) inhibitors designed to suppress diverse oncogenic variants of RAS proteins. The company’s RAS(ON) inhibitors daraxonrasib (RMC-6236), a RAS(ON) multi-selective inhibitor; elironrasib (RMC-6291), a RAS(ON) G12C-selective inhibitor; and zoldonrasib (RMC-9805), a RAS(ON) G12D-selective inhibitor, are currently in clinical development. The company anticipates that RMC-5127, a RAS(ON) G12V-selective inhibitor, will be its next RAS(ON) inhibitor to enter clinical development. Additional development opportunities in the company’s pipeline focus on RAS(ON) mutant-selective inhibitors, including RMC-0708 (Q61H) and RMC-8839 (G13C). For more information, please visit www.revmed.com and follow us on LinkedIn. Forward Looking Statements This press release contains forward-looking statements within the meaning of the U.S. Private Securities Litigation Reform Act of 1995. Any statements in this press release that are not historical facts may be considered "forward-looking statements," including without limitation statements regarding progression of clinical studies and findings from these studies, including the safety, tolerability and antitumor activity of the company’s candidates being studied and the durability of these results; the therapeutic potential of elironrasib; the ability of the company’s product engine to generate potential treatment approaches. Forward-looking statements are typically, but not always, identified by the use of words such as "may," "will," "would," "believe," "intend," "plan," "anticipate," "estimate," "expect," and other similar terminology indicating future results. Such forward-looking statements are subject to substantial risks and uncertainties that could cause the company’s development programs, future results, performance or achievements to differ materially from those anticipated in the forward-looking statements. Such risks and uncertainties include without limitation risks and uncertainties inherent in the drug development process, including the company’s programs’ current stage of development, the process of designing and conducting preclinical and clinical trials, risks that the results of prior clinical trials may not be predictive of future clinical trials, clinical efficacy, or other future results, the regulatory approval processes, the timing of regulatory filings, the challenges associated with manufacturing drug products, the company’s ability to successfully establish, protect and defend its intellectual property, other matters that could affect the sufficiency of the company’s capital resources to fund operations, reliance on third parties for manufacturing and development efforts, changes in the competitive landscape, and the effects on the company’s business of the global events, such as international conflicts or global pandemics. For a further description of the risks and uncertainties that could cause actual results to differ from those anticipated in these forward-looking statements, as well as risks relating to the business of Revolution Medicines in general, see Revolution Medicines’ Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission (the “SEC”) on May 7, 2025, and its future periodic reports to be filed with the SEC. Except as required by law, Revolution Medicines undertakes no obligation to update any forward-looking statements to reflect new information, events or circumstances, or to reflect the occurrence of unanticipated events. Revolution Medicines Media & Investor Contact:media@revmed.cominvestors@revmed.com 1 American Cancer Society. What is Lung Cancer. Available at: https://www.cancer.org/cancer/types/lung-cancer/about/what-is.html. Accessed July 2025. 2 National Cancer Institute. Non-Small Cell Lung Cancer Treatment. Available at: https://www.cancer.gov/types/lung/hp/non-small-cell-lung-treatment-pdq. Accessed July 2025. 3 Reita D, Pabst L., Pencreach E, et al. Direct Targeting KRAS Mutation in Non-Small Cell Lung Cancer: Focus on Resistance. Cancers (Basel). 2022; 14(15):1321. doi: 10.3390/cancers14051321 4 American Cancer Society. Key Statistics for Lung Cancer. Available at: https://www.cancer.org/cancer/types/lung-cancer/about/key-statistics.html. Accessed July 2025.