Hardy Thomas, Liang Su, Tedeschi Philip, Lin E, Brinton Eliot A, Davidson Michael H
Immunovant, Inc., 320 W 37th Street, 6th Floor, New York, NY, 10018, USA.
Utah Lipid Center, Salt Lake City, UT, USA.
Drug Saf. 2025 Apr 26. doi: 10.1007/s40264-025-01549-2.
Batoclimab is an anti-neonatal fragment crystallizable receptor monoclonal antibody in clinical development for the treatment of autoimmune diseases. In phase II trials, batoclimab resulted in dose-dependent reductions in pathogenic immunoglobulin G autoantibodies; however, dose-related increases in low-density lipoprotein cholesterol and other lipids were observed.
This study examined the relationship between batoclimab treatment and lipid levels, and whether increases in low-density lipoprotein cholesterol could be mitigated by coadministration with atorvastatin, a widely used cholesterol-lowering agent.
In this phase I, randomized, fixed-sequence, single-blind trial, 70 healthy participants received subcutaneous injections of batoclimab at various doses or placebo for 6 weeks. Open-label oral atorvastatin was coadministered in a subset of participants receiving batoclimab 340 mg or 680 mg weekly, starting 14 days before the first dose of the study drug, and continuing through the 6-week treatment period and 8-week safety follow-up. Key endpoints included changes in lipid parameters and atorvastatin pharmacokinetics.
Dose-dependent increases in total cholesterol and low-density lipoprotein cholesterol were observed with batoclimab doses ≥ 255 mg weekly, comparable to previous observations, whereas coadministration of atorvastatin 10 mg or 40 mg daily mitigated these changes. Batoclimab had little effect on atorvastatin pharmacokinetics. Dose-dependent decreases in serum albumin up to 37% were observed with batoclimab doses ≥ 255 mg weekly, returning to near-baseline levels 4 weeks after stopping batoclimab. As expected, coadministration of atorvastatin did not meaningfully impact the albumin level. The majority of adverse events were mild in severity.
Atorvastatin can mitigate clinically significant increases in low-density lipoprotein cholesterol that may occur with batoclimab treatment.
巴托昔单抗是一种抗新生儿可结晶片段受体单克隆抗体，正处于治疗自身免疫性疾病的临床开发阶段。在II期试验中，巴托昔单抗使致病性免疫球蛋白G自身抗体呈剂量依赖性降低；然而，观察到低密度脂蛋白胆固醇和其他脂质出现与剂量相关的升高。
本研究考察了巴托昔单抗治疗与血脂水平之间的关系，以及与广泛使用的降胆固醇药物阿托伐他汀联合使用是否可以减轻低密度脂蛋白胆固醇的升高。
在这项I期随机、固定序列、单盲试验中，70名健康参与者接受了不同剂量的巴托昔单抗皮下注射或安慰剂注射，为期6周。在一部分每周接受340 mg或680 mg巴托昔单抗治疗的参与者中，从研究药物第一剂前14天开始，同时给予开放标签的口服阿托伐他汀，并持续整个6周治疗期和8周安全随访期。主要终点包括血脂参数变化和阿托伐他汀的药代动力学。
观察到每周巴托昔单抗剂量≥255 mg时，总胆固醇和低密度脂蛋白胆固醇呈剂量依赖性升高，与之前的观察结果相当，而每日联合使用10 mg或40 mg阿托伐他汀可减轻这些变化。巴托昔单抗对阿托伐他汀的药代动力学影响较小。观察到每周巴托昔单抗剂量≥255 mg时，血清白蛋白剂量依赖性降低高达37%，在停用巴托昔单抗4周后恢复至接近基线水平。正如预期的那样，联合使用阿托伐他汀对白蛋白水平没有显著影响。大多数不良事件的严重程度为轻度。
阿托伐他汀可以减轻巴托昔单抗治疗可能导致的临床上显著的低密度脂蛋白胆固醇升高。
