美国市场撤市后日本和欧洲继续批准抗癌药物:加速批准的比较研究。
Continued cancer drug approvals in Japan and Europe after market withdrawal in the United States: A comparative study of accelerated approvals.
机构信息
Interfaculty Institute of Biochemistry, University of Tuebingen, Tuebingen, Germany.
Institute for Pharmaceutical and Social Health Sciences, Ise, Japan.
出版信息
Clin Transl Sci. 2024 Jul;17(7):e13879. doi: 10.1111/cts.13879.
Regulatory authorities must balance ensuring evidence of efficacy and safety of new drugs. Various regulatory pathways, such as the accelerated approval program in the United States (US), allow authorities to quickly approve drugs for severely ill patients by granting market authorization based on surrogate end points and pending confirmatory trials. In this cross-sectional study, we considered 23 indications of cancer drugs that received accelerated approval by the US Food and Drug Administration (FDA) but were subsequently withdrawn as of April 2023. Our investigation extended to assessing the regulatory status of these accelerated approvals in the European Union (EU) and Japan, examining relevant regulatory documents and identifying factors contributing to the withdrawal in the United States. Comparing regions, we found that for 52% (12/23) and 30% (7/23) of withdrawn accelerated approvals in the United States, sponsors had also sought marketing authorization from the European Medicines Agency (EMA) and Japan's Pharmaceuticals and Medical Devices Agency (PMDA), respectively. As of the April 30, 2023 study cutoff date, 83% (10/12) of drug-indication pairs remained approved by the EMA, while the PMDA retained 100% (7/7). For these indications, the time from FDA withdrawal until the study cutoff date ranged from 0.23 years to 11.45 years for EMA approvals (median: 1.28 years) and 1.10 years to 11.45 years for PMDA approvals (median: 3.22 years). These findings highlight substantial regulatory discrepancies concerning cancer drugs with unconfirmed benefits. Addressing these discrepancies may involve requiring pharmaceutical companies to confirm clinical benefits using more robust end points and fostering international harmonization in regulators' assessment.
监管机构必须平衡确保新药的疗效和安全性。各种监管途径,如美国的加速批准程序,允许当局通过基于替代终点和待确认试验的市场授权,快速批准用于重病患者的药物。在这项横断面研究中,我们考虑了截至 2023 年 4 月,美国食品和药物管理局 (FDA) 批准的用于癌症的 23 种适应证药物,但随后被撤回的适应证药物。我们的调查还扩展到评估这些加速批准在欧盟和日本的监管状况,审查相关监管文件,并确定导致在美国撤回的因素。比较各地区,我们发现对于美国 52%(12/23)和 30%(7/23)的撤回加速批准药物,赞助商还分别向欧洲药品管理局 (EMA) 和日本药品和医疗器械管理局 (PMDA) 寻求了营销授权。截至 2023 年 4 月 30 日的研究截止日期,EMA 仍批准了 83%(10/12)的药物-适应证对,而 PMDA 保留了 100%(7/7)。对于这些适应证,从 FDA 撤回到研究截止日期的时间范围,EMA 批准的时间从 0.23 年到 11.45 年不等(中位数:1.28 年),PMDA 批准的时间从 1.10 年到 11.45 年不等(中位数:3.22 年)。这些发现突出了未证实获益的癌症药物存在实质性监管差异。解决这些差异可能涉及要求制药公司使用更可靠的终点来确认临床获益,并促进监管机构评估的国际协调。