EMA建议批准Rasonque用于转移性胰腺癌
正文 · 中文译文
欧洲药品管理局（EMA）的人用药品委员会（CHMP）已建议在欧盟授予Rasonque（daraxonrasib）的上市许可，该药是一种口服治疗药物，用于既往接受过至少一种治疗的成人转移性胰腺腺癌（已扩散的胰腺癌）患者。 转移性胰腺腺癌患者若既往治疗后病情恶化，其治疗选择有限，预后较差。鉴于该疾病的严重性、标准化疗方案疗效有限且毒性较大，这些患者需要更好的治疗选择。 EMA的这一建议是在对Rasonque的数据进行分阶段审查后提出的，该药物在EMA的“癌症药物探路者”项目中被认定为可能满足这一未满足医疗需求的高优先级药物。 分阶段审查使CHMP得以在完整申请预计提交前数月即启动评估。在始于2026年7月初的审查过程中，CHMP按公司提交数据的阶段，分阶段评估了质量、非临床和临床数据。这种方法将评估时间缩短至不到150天，同时保持了质量、安全性和有效性的标准。相比之下，标准评估可能需要长达210个活跃日，通常总共需要约一年时间，其中包括公司答复问题的时间。 对Rasonque分阶段审查中吸取的经验教训，将有助于为欧盟新药品立法下分阶段审查的实施和加强使用提供信息。在此背景下，分阶段审查被视为一种工具，可对药品进行更灵活、更简化的评估，最终使患者更早获得有前景的治疗。 Rasonque中的活性物质daraxonrasib是一种RAS抑制剂。RAS蛋白参与细胞生长和存活。在胰腺腺癌中，RAS基因的突变导致这些蛋白永久激活，导致癌细胞不受控制地生长。Daraxonrasib通过与一种名为亲环蛋白A的蛋白结合形成复合物，该复合物附着于RAS蛋白，阻断其活性。这能杀死癌细胞并减缓癌症生长。 Rasonque在一项开放标签、3期、多国研究中接受了评估，该研究涉及500名转移性胰腺腺癌患者，这些患者在此前接受过全身治疗（全身性治疗）后病情出现恶化。在这些患者中，92%的患者已确认为RAS G12突变，其中包括与这种疾病相关的最常见的RAS突变。接受Rasonque治疗的患者中位总生存期为12.4个月，而接受化疗的患者为6.7个月。此外，接受Rasonque治疗的患者中位无疾病恶化生存期为7.2个月，而接受化疗的患者为3.6个月（数据截止日期见注3）。Rasonque报告的最常见副作用为腹泻、皮疹、口腔炎（口腔黏膜炎症）、恶心和呕吐。 CHMP采纳的意见是Rasonque通向患者可及性道路上的一个中间步骤。该意见现将被提交至欧盟委员会，欧盟委员会将快速审批关于Rasonque在全欧盟范围内上市许可的决定。一旦获得上市许可，价格和报销决定将在各成员国层面进行，同时考虑该药物在该国国家卫生体系背景下可能发挥的作用或用途。 展望未来，欧洲药品管理局（EMA）与人用药品委员会（CHMP）达成一致，将在可行且预期能加速评估的情况下，考虑对正在研发中的其他药品进行分阶段审评。这将基于具体情况逐案决定，依据是该药品是否可能满足未获满足的医疗需求，以及从公共卫生角度来看，特别是就治疗创新性而言，是否预期具有重大意义。 Rasonque（daraxonrasib）的申请人为Revolution Medicines公司。 Daraxonrasib于2026年4月20日被指定为治疗胰腺癌的孤儿药。 总生存期分析基于截至2026年6月15日收集的数据；无进展生存期分析基于截至2026年2月10日收集的数据。 Daraxonrasib属于欧盟卫生技术评估法规的适用范围。联合临床评估独立于欧洲药品管理局（EMA）对上市许可申请的审评，由欧盟委员会内的卫生技术评估（HTA）秘书处协调。 Daraxonrasib：治疗胰腺癌的孤儿药认定 卫生技术评估机构：与HTA机构的欧洲层面合作 欧盟卫生技术评估法规——法规（EU）2021/2282 药品联合临床评估——欧盟委员会 电话：+31 (0)88 781 8427 邮箱：press@ema.europa.eu
正文 · 英文原文
EMA’s human medicines committee (CHMP) has recommended granting a marketing authorisation in the European Union for Rasonque (daraxonrasib), an oral treatment for adults with metastatic pancreatic adenocarcinoma (pancreatic cancer that has spread) who have received at least one previous treatment. People with metastatic pancreatic adenocarcinoma whose disease has worsened after prior treatment have limited treatment options and a poor prognosis. Given the seriousness of the disease, the limited efficacy and substantial toxicity of standard-of-care chemotherapy, there is a need for better treatment options for these patients. EMA’s recommendation follows a phased review of data on Rasonque, which was identified under EMA’s Cancer Medicines Pathfinder project as a high-priority medicine that could address this unmet medical need. The phased review allowed CHMP to start the assessment several months before the anticipated submission of the complete application. During the review, which started in early July 2026, the CHMP evaluated the data (quality, non-clinical and clinical) in phases, as they were submitted by the company. This approach shortened the assessment time to less than 150 days, while maintaining the standards for quality, safety and effectiveness. By comparison, a standard evaluation can take up to 210 active days and usually takes around a year overall, including time for the company to respond to questions. The lessons learnt from the phased review of Rasonque will help inform the implementation and strengthened use of phased reviews under the EU’s new pharmaceutical legislation . In this context, the phased review is foreseen as a tool to allow a more agile, streamlined evaluation of medicines, which would ultimately lead to earlier patient access to promising treatments. The active substance in Rasonque, daraxonrasib, is a RAS inhibitor. RAS proteins are involved in cell growth and survival. In pancreatic adenocarcinoma, mutations in the RAS gene cause these proteins to be permanently switched on, leading to uncontrolled growth of cancer cells. Daraxonrasib works by binding to a protein called cyclophilin A to form a complex that attaches to RAS proteins, blocking their activity. This kills cancer cells and slows cancer growth. Rasonque was investigated in an open-label, phase 3, multinational study involving 500 patients with metastatic pancreatic adenocarcinoma whose disease had worsened after prior systemic (whole-body) treatment. Of these patients, 92% had a confirmed RAS G12 mutation, which includes the most common RAS mutations associated with this disease. Patients treated with Rasonque lived for a median of 12.4 months, compared with 6.7 months for those treated with chemotherapy. In addition, the median time patients lived without their disease worsening was 7.2 months with Rasonque, compared with 3.6 months with chemotherapy (see Note 3 for data cut-off dates). The most common side effects reported with Rasonque were diarrhoea, rash, stomatitis (inflammation of the lining of the mouth), nausea and vomiting. The opinion adopted by the CHMP is an intermediary step on Rasonque’s path to patient access. The opinion will now be sent to the European Commission, which will fast-track the decision on an EU wide marketing authorisation for Rasonque. Once a marketing authorisation has been granted, decisions about price and reimbursement will take place at the level of each Member State, taking into account the potential role or use of this medicine in the context of the national health system of that country. Looking ahead, EMA, in agreement with the CHMP, will consider further medicines under development for phased review when this approach is feasible and expected to accelerate assessment. This will be decided on a case-by-case basis, based on whether the medicine is likely to address an unmet medical need and is expected to be of major interest from the point of view of public health, in particular as regards therapeutic innovation. The applicant for Rasonque (daraxonrasib) is Revolution Medicines. Daraxonrasib was designated an orphan medicinal product for the treatment of pancreatic cancer on 20 April 2026. Overall survival analysis based on data collected up to 15 June 2026; analysis of progression-free survival based on data collected up to 10 February 2026. Daraxonrasib falls under the scope of the EU Health Technology Assessment Regulation. The joint clinical assessment is independent of EMA’s review of the marketing authorisation application and is coordinated by the HTA Secretariat within the European Commission. Daraxonrasib: orphan designation for treatment of pancreatic cancer Health technology assessment bodies: European-level cooperation with HTA bodies EU Health Technology Assessment Regulation - Regulation (EU) 2021/2282 Joint clinical assessments for medicinal products - European Commission Tel. +31 (0)88 781 8427 E-mail: press@ema.europa.eu