Zhang Xin, Otani Yuki, Payne Christopher D, Morris Nathan J, Chua Laiyi, Escobar Rodrigo, Wang Sihe, Shi Galen
Eli Lilly and Company, Lilly Corporate Center, 893 Delaware Street, Indianapolis, IN, 46225, USA.
Adv Ther. 2025 Sep 3. doi: 10.1007/s12325-025-03335-z.
Mirikizumab, a humanized anti-interleukin-23p19 monoclonal antibody, is approved for the treatment of moderate-to-severe ulcerative colitis (UC) and Crohn's disease (CD). Two phase 1, open-label, two-arm, randomized studies compared pharmacokinetics and safety of mirikizumab (200 mg, Study AMBW; 300 mg, Study AMBX) to establish bioequivalence. Mirikizumab was administered subcutaneously using an autoinjector or a prefilled syringe (PFS) as a single dose in healthy participants.
Participants (male and female) were randomized 1:1 to mirikizumab by a PFS (reference) and an autoinjector (test). Participants were sub-randomized (1:1:1) to one of three injection sites (abdomen, arm, thigh) and stratified into one of three weight groups. Primary endpoints were maximum observed drug concentration (C), and area under concentration versus time curves (time zero to infinity [AUC]; time to last time point with measurable concentration [AUC]). Secondary objectives were safety and immunogenicity.
In Study AMBW, 90% confidence intervals (CIs) for the ratios (autoinjector to PFS) of geometric least squares mean values for C, AUC, and AUC were within prespecified bioequivalence limits (0.80-1.25). Similar results were observed in Study AMBX, after administration of mirikizumab 300 mg, with bioequivalence achieved for AUC and AUC, while the upper bound of the 90% CI of the geometric least squares mean ratio for C was slightly above the bioequivalence upper threshold. Overall safety of mirikizumab was similar between devices in both studies. Immunogenicity was similar overall in Study AMBW, but slightly higher (autoinjector versus PFS) in Study AMBX.
Mirikizumab administered by autoinjector or PFS was considered bioequivalent at the 200-mg UC maintenance dose and the 300-mg CD maintenance dose. Safety and immunogenicity profiles were comparable between autoinjector and PFS. Availability of an autoinjector option may be preferred by some patients and may help improve patient adherence to treatment.
ClinicalTrials.gov NCT04607733; NCT05069896.
mirikizumab是一种人源化抗白细胞介素-23p19单克隆抗体，已被批准用于治疗中度至重度溃疡性结肠炎（UC）和克罗恩病（CD）。两项1期开放标签双臂随机研究比较了mirikizumab（200mg，研究AMBW；300mg，研究AMBX）的药代动力学和安全性，以确定生物等效性。在健康参与者中，使用自动注射器或预填充注射器（PFS）皮下注射mirikizumab作为单剂量给药。
参与者（男性和女性）按1:1随机分为使用PFS（参比）和自动注射器（受试）的mirikizumab组。参与者再按1:1:1随机分为三个注射部位（腹部、手臂、大腿）之一，并分层为三个体重组之一。主要终点为最大观察药物浓度（Cmax）以及浓度-时间曲线下面积（从时间零点至无穷大[AUC∞]；至最后一个可测浓度时间点的曲线下面积[AUCt]）。次要目标为安全性和免疫原性。
在研究AMBW中，Cmax、AUC∞和AUCt的几何最小二乘均值比值（自动注射器与PFS）的90%置信区间（CI）在预先指定的生物等效性限度（0.80 - 1.25）内。在研究AMBX中，给予300mg mirikizumab后观察到类似结果，AUC∞和AUCt实现了生物等效性，而Cmax的几何最小二乘均值比值的90%CI上限略高于生物等效性上限阈值。在两项研究中，两种给药装置的mirikizumab总体安全性相似。在研究AMBW中免疫原性总体相似，但在研究AMBX中略高（自动注射器与PFS相比）。
在200mg UC维持剂量和300mg CD维持剂量下，通过自动注射器或PFS给药的mirikizumab被认为具有生物等效性。自动注射器和PFS的安全性和免疫原性特征具有可比性。自动注射器选项的可用性可能受到一些患者的青睐，并可能有助于提高患者的治疗依从性。
ClinicalTrials.gov NCT04607733；NCT05069896。
