Bermekimab是人源重组单克隆抗体,通过特异性阻断白介素-1α活性而表现出免疫调节活性。四项2期研究评估了Bermekimab在中度至重度特应性皮炎(AD)患者中的疗效和安全性。此外,开发了一种新型的人类皮肤外植体模型来评估Bermekimab的药代动力学/药效学和蛋白质组学/转录组学效应。研究1(NCT03496974,N=38)是开放标签,皮下bermekimab(200mg或400mg)的剂量递增研究。研究2(NCT04021862,N=87)是双盲,安慰剂对照,随机(1:1:1)研究皮下Bermekimab(每周400mg(qw)或每2周)或安慰剂。GENESIS(NCT04711319,N=198)为双盲,安慰剂和有源比较器控制,随机(1:1:2:2)安慰剂研究,皮下bermekimab(350毫克或700毫克qw),或者dupilumab.LUNA(NCT04990440,N=6)是双盲,安慰剂对照,随机(4:1)静脉注射Bermekimab800mgqw或安慰剂的研究。新的人离体皮肤药效学测定支持0期(NCT03953196)和1期(NCT04544813)研究。在研究1中,400毫克皮下bermekimab显示出疗效评估的改善(例如,EASI比基线改善≥75%,IGA0/1,最瘙痒);但是,在研究2或GENESIS中未证实疗效.因此,GENESIS和LUNA提前终止。新的人离体皮肤药效学测定证明bermekimab降低了下游皮肤损伤反应。尽管bermekimab在临床前和早期开放标签试验中显示出作为AD治疗的潜力,较大的对照研究(研究2和GENESIS)未证实这些初步结果.
Bermekimab is a human-derived recombinant monoclonal antibody that exhibits immunoregulatory activity by specifically blocking interleukin-1α activity. Four phase 2 studies evaluated efficacy and safety of bermekimab in patients with moderate-to-severe atopic dermatitis (AD). In addition, a novel human skin explant model was developed to assess bermekimab pharmacokinetics/pharmacodynamics and proteomic/transcriptomic effects. Study 1 (NCT03496974, N = 38) was an open-label, dose escalation study of
subcutaneous bermekimab (200 mg or 400 mg). Study 2 (NCT04021862, N = 87) was a double-blind, placebo-controlled, randomized (1:1:1) study of
subcutaneous bermekimab (400 mg every week (qw) or every 2 weeks) or placebo. GENESIS (NCT04791319, N = 198) was a double-blind, placebo- and active-comparator-controlled, randomized (1:1:2:2) study of placebo,
subcutaneous bermekimab (350 mg or 700 mg qw), or dupilumab. LUNA (NCT04990440, N = 6) was a double-blind, placebo-controlled, randomized (4:1) study of intravenous bermekimab 800 mg qw or placebo. A novel human ex vivo skin pharmacodynamic assay supported phase 0 (NCT03953196) and phase 1 (NCT04544813) studies. In Study 1, 400 mg
subcutaneous bermekimab showed improvement in efficacy assessments (e.g., ≥ 75% improvement of EASI over baseline, IGA 0/1, and worst itch); however, efficacy was not confirmed in Study 2 or GENESIS. Consequently, GENESIS and LUNA were terminated early. The novel human ex vivo skin pharmacodynamic assay demonstrated that bermekimab reduced downstream skin injury responses. Although bermekimab showed potential as an AD treatment in preclinical and early open-label trials, larger controlled studies (Study 2 and GENESIS) did not confirm those initial results.