Washington University School of Medicine, St Louis, MO, USA.
Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Clin Drug Investig. 2020 Oct;40(10):973-983. doi: 10.1007/s40261-020-00958-8.
Technosphere Insulin (TI), a human insulin powder for inhalation (Afrezza; MannKind Corporation, Westlake Village, CA, USA), is an ultra-rapid-acting inhaled insulin indicated to improve postprandial glycemic control in patients with type 1 or type 2 diabetes mellitus (T1DM or T2DM). Because TI is absorbed across the alveolar membrane, the objective of this analysis was to characterize its pulmonary safety.
Pooled data from 13 phase 2/3 clinical studies in 5505 patients with T1DM or T2DM treated with TI, Technosphere inhalation powder without insulin (TP; placebo), or active-comparator treatment were analyzed for incidences of respiratory treatment-emergent adverse events (TEAEs), changes in pulmonary function, and lung malignancies. Radiographic changes in the lungs were monitored in a subset of 229 patients.
Among 3017 patients receiving TI, the median duration of TI exposure was 168 days; median active-comparator and TP exposure durations were 363 and 149 days for 2198 and 290 patients, respectively. Respiratory TEAEs were comparable across treatments, except for a higher incidence of mild cough with TI in active-comparator studies (28.0% vs. 5.2%). Slight reversible declines in pulmonary function from baseline were observed for TI versus TP and active-comparator treatments, including in a subpopulation of patients with retrospectively identified lung dysfunction. Lung malignancies were reported in two patients on active TI therapy with a smoking history. No clinically significant changes from baseline were observed in radiographic images.
Pulmonary safety assessment of the TI inhalation system did not identify any safety issues in individuals with either T1DM or T2DM.
Technosphere Insulin（TI），一种用于吸入的人胰岛素粉末（Afrezza；MannKind Corporation，加利福尼亚州西湖村），是一种超快速作用的吸入胰岛素，用于改善 1 型或 2 型糖尿病（T1DM 或 T2DM）患者的餐后血糖控制。由于 TI 通过肺泡膜吸收，因此本分析的目的是描述其肺部安全性。
对接受 TI、Technosphere 吸入粉末无胰岛素（TP；安慰剂）或活性对照治疗的 5505 例 T1DM 或 T2DM 患者的 13 项 2/3 期临床研究的汇总数据进行分析，以评估呼吸治疗新发不良事件（TEAEs）、肺功能变化和肺部恶性肿瘤的发生率。在 229 例患者的亚组中监测肺部的放射学变化。
在接受 TI 治疗的 3017 例患者中，TI 暴露的中位时间为 168 天；中位活性对照和 TP 暴露时间分别为 363 和 149 天，分别用于 2198 和 290 例患者。除了在活性对照研究中 TI 更常见轻度咳嗽（28.0%对 5.2%）外，各治疗组的呼吸 TEAEs 相当。与 TP 和活性对照治疗相比，TI 治疗后肺功能出现轻微可逆下降，包括在回顾性确定有肺功能障碍的患者亚群中。两名有吸烟史的 TI 治疗患者报告了肺部恶性肿瘤。从基线到放射图像没有观察到任何临床显著变化。
TI 吸入系统的肺部安全性评估未在 T1DM 或 T2DM 患者中发现任何安全性问题。
