Luo Xingxian, Du Xin, Huang Lin, Guo Qixiang, Tan Ruijie, Zhou Yue, Li Zhuangqi, Xue Xuecai, Li Taifeng, Le Kaidi, Qian Feng, Chow Shein-Chung, Yang Yue
School of Pharmaceutical Sciences, Tsinghua University, Beijing, China.
Key Laboratory of Innovative Drug Research and Evaluation, National Medical Products Administration, Beijing, China.
Lancet Reg Health West Pac. 2022 Dec 28;32:100670. doi: 10.1016/j.lanwpc.2022.100670. eCollection 2023 Mar.
Affordability to novel anticancer drugs has become a major health issue in China. It is encouraging to note that China initiated its drug regulatory reform and national price negotiation policies since 2015. As a growing number of domestic within-class targeted anticancer drugs are approved in China, it is expected that this may reduce the price of novel anticancer drugs and improve the affordability of anticancer drugs. This study aimed to evaluate the price, efficacy, and safety of the within-class anticancer drugs between domestic and imported drugs approved in China from 2010 to 2022.
The domestic and imported within-class targeted drugs for solid cancers approved in China between 2010 and 2022 were extracted. We classified it as a class of anticancer drugs based on the same indication and similar biological mechanism. The published literature derived from pivotal clinical trials of these domestic and imported drugs was identified based on the review report and the latest labels issued by the China National Medical Products Administration. We evaluated the monthly treatment price at launch and the latest (2022), primary efficacy endpoint and safety between domestic and imported anticancer drugs. Meta-analyses were further employed to evaluate the efficacy and safety of the domestic and imported anticancer drugs, including pooled hazard ratios (HR) for progression-free survival (PFS), overall survival (OS), objective response rates (ORR) for solid cancers, and relative risk for serious adverse events (SAE) and Grade ≥3 adverse events (AEs).
In our cohort study, 12 within-class anticancer drugs with 7 cancer diseases were analyzed, including 18 domestic (21 indications; 21 pivotal trials) and 18 imported (21 indications; 27 pivotal trials) novel anticancer drugs, respectively. The median monthly treatment price of domestic and imported drugs from the years of launch to 2022 had significantly decreased by 71% and 62%, respectively. Moreover, the median monthly treatment price of domestic targeted anticancer drugs on the market at launch ($3786 vs. $5393, = 0.007) and the latest ($1222 vs. $2077, = 0.011) was significantly lower than that of imported drugs. No significant differences in median PFS gains (9.0 vs. 11.0 months; = 0.24), OS gains (9.3 vs 10.6 months; = 0.66), and ORR (57% vs 62%, = 0.77) of targeted anticancer drugs in their pivotal trials were observed between the domestic and imported drugs. Additionally, there was no significant difference between domestic and imported drugs in the incidence of SAE (23% vs. 24%; = 0.41) and Grade ≥3 AEs (59% vs. 57%; = 0.45). These findings were also further confirmed in the meta-analyses for primary efficacy endpoints and safety outcomes.
The prices of both domestic and imported anticancer drugs significantly decreased after market entry mainly due to the role of national price negotiations. The median monthly treatment price of domestic within-class targeted anticancer drugs was significantly lower than that of imported drugs. Furthermore, the efficacy and safety of domestic anticancer drugs were comparable to that of imported drugs. This evidence implicated that the development of within-class anticancer drugs with national price negotiations in China significantly improved the affordability for patients.
This study was supported by postdoctoral fellowship from Tsinghua-Peking Joint Centers for Life Sciences (CLS).
新型抗癌药物的可及性已成为中国的一个主要健康问题。令人鼓舞的是，自2015年以来中国启动了药品监管改革和国家价格谈判政策。随着越来越多国内同类靶向抗癌药物在中国获批，预计这可能会降低新型抗癌药物的价格并提高抗癌药物的可及性。本研究旨在评估2010年至2022年在中国获批的国产与进口同类抗癌药物的价格、疗效和安全性。
提取2010年至2022年在中国获批的国产和进口同类实体癌靶向药物。我们根据相同适应症和相似生物学机制将其归类为一类抗癌药物。基于中国国家药品监督管理局发布的审评报告和最新说明书，确定这些国产和进口药物关键临床试验的已发表文献。我们评估了上市时和最新（2022年）的每月治疗价格、国产与进口抗癌药物之间的主要疗效终点和安全性。进一步采用荟萃分析评估国产和进口抗癌药物的疗效和安全性，包括无进展生存期（PFS）、总生存期（OS）的合并风险比（HR）、实体癌的客观缓解率（ORR）以及严重不良事件（SAE）和≥3级不良事件（AE）的相对风险。
在我们的队列研究中，分析了12种针对7种癌症疾病的同类抗癌药物，分别包括18种国产（21个适应症；21项关键试验）和18种进口（21个适应症；27项关键试验）新型抗癌药物。从上市年份到2022年，国产和进口药物的每月治疗价格中位数分别显著下降了71%和62%。此外，上市时（3786美元对5393美元，P = 0.007）和最新（1222美元对2077美元，P = 0.011）国产靶向抗癌药物的每月治疗价格中位数显著低于进口药物。在关键试验中，国产与进口靶向抗癌药物的PFS获益中位数（9.0对11.0个月；P = 0.24）、OS获益中位数（9.3对10.6个月；P = 0.66）和ORR（57%对62%，P = 0.77）未观察到显著差异。此外，国产与进口药物在SAE发生率（23%对24%；P = 0.41）和≥3级AE发生率（59%对57%；P = 0.45）方面也没有显著差异。这些结果在主要疗效终点和安全性结果的荟萃分析中也得到了进一步证实。
国产和进口抗癌药物上市后价格均显著下降，主要归因于国家价格谈判的作用。国产同类靶向抗癌药物的每月治疗价格中位数显著低于进口药物。此外，国产抗癌药物的疗效和安全性与进口药物相当。这一证据表明，中国通过国家价格谈判开发同类抗癌药物显著提高了患者可及性。
本研究得到了清华-北大生命科学联合中心（CLS）博士后奖学金的支持。
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