Deiteren Annemie, Krupka Emmanuel, Bontinck Lieselot, Imberdis Karine, Conickx Griet, Bas Selcuk, Patel Naimish, Staudinger Heribert W, Suratt Benjamin T
Sanofi, Ghent, Belgium
Sanofi, Montpellier, France.
Eur Respir J. 2025 Apr 24;65(4). doi: 10.1183/13993003.01461-2024. Print 2025 Apr.
Monovalent biologics blocking thymic stromal lymphopoietin (TSLP) or interleukin (IL)-13 have been shown to elicit pharmacodynamic responses in asthma following a single dose. Therefore, dual blockade of these cytokines may result in an enhanced response compared to single targeting and has the potential to break efficacy ceilings in asthma. This study assessed the safety and tolerability of lunsekimig, a bispecific NANOBODY molecule that blocks TSLP and IL-13, and its effect on type 2 (T2) inflammatory biomarkers and lung function in asthma.
This was a phase 1b, single-dose (subcutaneous lunsekimig 400 mg or placebo), randomised (2:1), double-blind, proof-of-mechanism study in 36 participants with mild-to-moderate asthma and elevated exhaled nitric oxide fraction ( ; ≥25 ppb), a marker of airway inflammation. The primary end-point was safety and tolerability through day 71. The main pharmacodynamic secondary end-point was change from baseline in at day 29.
Lunsekimig was well tolerated, with no serious treatment-emergent adverse events. was significantly reduced from day 8 through day 29 after a single dose, with change from baseline of -40.9 (90% CI -55.43- -26.39) ppb (p<0.0001) placebo at day 29. Blood-based T2 biomarkers at day 29 were significantly reduced from baseline. Lung function, particularly small airway dysfunction, was numerically improved at day 29, most notably in participants with impaired lung function at baseline.
A single dose of lunsekimig was well tolerated, significantly suppressed T2 inflammation and improved lung function in mild-to-moderate asthma.
单克隆生物制剂阻断胸腺基质淋巴细胞生成素（TSLP）或白细胞介素（IL）-13已被证明在单次给药后可引发哮喘患者的药效学反应。因此，与单一靶点相比，双重阻断这些细胞因子可能会增强反应，并有可能突破哮喘治疗的疗效上限。本研究评估了阻断TSLP和IL-13的双特异性纳米抗体分子伦塞基米（lunsekimig）的安全性和耐受性，及其对哮喘患者2型（T2）炎症生物标志物和肺功能的影响。
这是一项1b期单剂量（皮下注射400mg伦塞基米或安慰剂）、随机（2:1）、双盲、机制验证研究，纳入36例轻度至中度哮喘且呼出气一氧化氮分数升高（；≥25ppb）的参与者，呼出气一氧化氮分数是气道炎症的标志物。主要终点是至第71天的安全性和耐受性。主要药效学次要终点是第29天时与基线相比的变化。
伦塞基米耐受性良好，未出现严重的治疗中出现的不良事件。单次给药后，从第8天至第29天显著降低，第29天时与安慰剂相比，基线变化为-40.9（90%CI -55.43--26.39）ppb（p<0.0001）。第29天时基于血液的T2生物标志物与基线相比显著降低。第29天时肺功能，尤其是小气道功能障碍在数值上有所改善，在基线肺功能受损的参与者中最为明显。
单剂量伦塞基米耐受性良好，可显著抑制轻度至中度哮喘患者的T2炎症并改善肺功能。
