Qin Albert, Wu Daoxiang, Li Yaning, Zhang Jingjing, Wang Wei, Shen Weihong, Liao Jason, Lin Sheena, Chang Cynthia, Chen Haoqi, Cui Jie, Su Xia
Medical Research & Clinical Operations, PharmaEssentia Corporation, Taipei, Taiwan, ROC.
PharmaEssentia Biotech (Beijing) Limited, Beijing, China.
Br J Clin Pharmacol. 2024 Jun;90(6):1493-1502. doi: 10.1111/bcp.16043. Epub 2024 Mar 19.
To investigate the exposure-response (E-R) relationship, including exposure-efficacy and exposure-safety, of ropeginterferon alfa-2b treatment in patients with polycythaemia vera (PV).
Based on the results of the phase II trial A20-202 regarding ropeginterferon alfa-2b in patients with PV, E-R analyses were performed to evaluate the efficacy and safety of the given dosing regimen. The E-R analyses were based on logistic and linear regression and the relationship between exposure to ropeginterferon alfa-2b and key efficacy and safety variables. The key efficacy variables included complete haematologic response (CHR) and reduction of the driver mutation JAK2V617F. The safety variable was treatment-related adverse events (TRAEs).
A clear relationship between the exposure to ropeginterferon alfa-2b and CHR was observed, with an increase in drug exposure resulting in an increased probability of achieving CHR. Similar CHR probabilities were observed in the third and fourth quantiles of the average concentration at Week 24. The results from the exposure-JAK2V617F model indicated that the JAK2V617F allele burden decreased with increasing exposure to ropeginterferon alfa-2b and baseline body surface area. Exposure-safety analysis revealed a risk of AEs associated with transaminase abnormalities, which were not associated with clinical significance.
Our analyses have shown that patients with PV treated with ropeginterferon alfa-2b had an increased probability of achieving CHR and a molecular response with acceptable safety risks at the 250-350-500 μg titration dosing regimen. This study has provided the relevant data for the application of a biologics licence of ropeginterferon alfa-2b for PV treatment in China.
研究聚乙二醇干扰素α-2b治疗真性红细胞增多症（PV）患者的暴露-反应（E-R）关系，包括暴露-疗效和暴露-安全性。
基于关于聚乙二醇干扰素α-2b治疗PV患者的II期试验A20-202的结果，进行E-R分析以评估给定给药方案的疗效和安全性。E-R分析基于逻辑回归和线性回归以及聚乙二醇干扰素α-2b暴露与关键疗效和安全性变量之间的关系。关键疗效变量包括完全血液学缓解（CHR）和驱动基因突变JAK2V617F的减少。安全性变量是治疗相关不良事件（TRAEs）。
观察到聚乙二醇干扰素α-2b暴露与CHR之间存在明确关系，药物暴露增加导致实现CHR的概率增加。在第24周平均浓度的第三和第四分位数中观察到相似的CHR概率。暴露-JAK2V617F模型的结果表明，JAK2V617F等位基因负担随着聚乙二醇干扰素α-2b暴露和基线体表面积的增加而降低。暴露-安全性分析揭示了与转氨酶异常相关的不良事件风险，这些异常不具有临床意义。
我们的分析表明，在250-350-500μg滴定给药方案下，聚乙二醇干扰素α-2b治疗的PV患者实现CHR的概率增加，且分子反应具有可接受的安全风险。本研究为聚乙二醇干扰素α-2b在中国PV治疗的生物制品许可申请提供了相关数据。
