Efficacy and safety of iscalimab, a novel anti-CD40 monoclonal antibody, in moderate-to-severe myasthenia gravis: A phase 2 randomized study

被引：10

作者：

GomezMancilla, Baltazar ^{[1
]}

Meriggioli, Matthew N. ^{[2
,17
]}

Genge, Angela ^{[3
]}

Roubenoff, Ronenn ^{[1
]}

Espie, Pascal ^{[1
,5
]}

Dupuy, Cyrielle ^{[1
]}

Hartmann, Nicole ^{[1
]}

Pezous, Nicole ^{[1
]}

Kinhikar, Arvind ^{[4
]}

Tichy, Mia ^{[1
]}

Dionne, Annie ^{[5
]}

Vissing, John ^{[6
]}

Andersen, Henning ^{[7
]}

Schoser, Benedikt ^{[8
]}

Meisel, Andreas ^{[9
]}

Jordan, Berit ^{[10
,11
]}

Devlikamova, Farida ^{[12
]}

Poverennova, Irina ^{[13
]}

Stuchevskaya, Fatima ^{[14
]}

Lin, Thy-Sheng ^{[15
]}

Rush, James S. ^{[1
,16
]}

Gergely, Peter ^{[1
]}

机构：

[1] Novartis Inst Biomed Res, Basel, Switzerland

[2] Novartis Inst Biomed Res, Cambridge, MA USA

[3] Montreal Neurol Hosp & Inst, Montreal, PQ, Canada

[4] Novartis Inst Biomed Res, Cambridge, MA USA

[5] Univ Laval, CHU Quebec, Quebec City, PQ, Canada

[6] Univ Copenhagen, Rigshosp, Copenhagen, Denmark

[7] Aarhus Univ Hosp, Aarhus, Denmark

[8] Friedrich Baur Inst, LMU Klinikum Muenchen, Dep Neurol, Munich, Germany

[9] Charite Univ Med Berlin, Dept Neurol, Berlin, Germany

[10] Univ Hosp Halle, Dept Neurol, Halle, Germany

[11] Univ Hosp Heidelberg, Dept Neurol, Heidelberg, Germany

[12] Republican Clin Hosp Med Rehabil, Kazan, Russia

[13] Samara Reg Clin Hosp, Samara, Russia

[14] City Multispecialty Hosp, St Petersburg, Russia

[15] Natl Cheng Kung Univ Hosp, Tainan, Taiwan

[16] Kling Biotherapeuet BV, Amsterdam, Netherlands

[17] Translat Med EH, Novartis Biomed Res, Cambridge, MA 02139 USA

来源：

JOURNAL OF CLINICAL NEUROSCIENCE | 2024年 / 119卷

关键词：

Anti-CD40 monoclonal antibody clinical trial; Efficacy; Iscalimab; Myasthenia gravis; Safety; QUALITY-OF-LIFE; CELLS;

D O I：

10.1016/j.jocn.2023.11.013

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

Background: Increased morbidity in many patients with myasthenia gravis (MG) on long-term immunosuppression highlights the need for improved treatments. The aim of this study is to investigate the safety and efficacy of iscalimab (CFZ533), a fully human anti-CD40 monoclonal antibody, in patients with moderate-to-severe MG receiving standard-of-care (SoC) therapies.Methods: In this double-blind, placebo-controlled phase 2 study, symptomatic patients (n = 44) despite SoC were randomized 1:1 to receive intravenous iscalimab (10 mg/kg; n = 22) or placebo (n = 22) every 4 weeks for 6 doses in total. Patients were followed up for 6 months after the last dose. The total duration of the study was 52 weeks.Results: In total, 34 of 44 patients (77.3 %) completed the study. The primary endpoint, Quantitative MG score, did not change significantly between baseline and week 25 for iscalimab (median [90 % CI], -4.07 [-5.67, -2.47]) versus placebo (-2.93 [-4.53, -1.33]); however, non-thymectomized patients (n = 29) showed more favorable results (iscalimab, -4.35 [-6.07, -2.64] vs placebo, -2.26 [-4.16, -0.36]). A statistically significant difference between iscalimab and placebo groups was observed in MG Composite score (adjusted mean change: -4.19 [-6.67, -1.72]; p = 0.007) at week 13, and MG-Activities of Daily Living score (-1.93 [-3.24, -0.62]; p = 0.018) at week 21. Adverse events were comparable between the iscalimab (91 %) and placebo (96 %) groups.Conclusion: Iscalimab showed favorable safety and improvements compared with placebo in non-thymectomized patients with moderate-to-severe MG. It did not show any protective effect in patients with moderate-to-severe MG.

引用

页码：76 / 84

页数：9

共 33 条

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