Sacramento Ear, Nose, and Throat, Roseville, California.
Advanced ENT and Allergy, Louisville, Kentucky.
Am J Rhinol Allergy. 2022 Nov;36(6):733-740. doi: 10.1177/19458924221107200. Epub 2022 Jun 16.
The efficacy of topical corticosteroids is limited in chronic rhinosinusitis (CRS) due to rapid clearance from the nasal cavity and insufficient drug delivery to inflamed sinonasal passages. LYR-210 is an implantable corticosteroid matrix designed to provide up to 24 weeks of treatment to patients with CRS by locally delivering mometasone furoate (MF) to the sinonasal mucosa. In a randomized, controlled, dose-ranging LANTERN study, LYR-210 (7500 µg) achieved clinically relevant improvement in CRS cardinal symptom composite scores, the 22-item Sinonasal Outcome Test (SNOT-22), ethmoid opacification, and the need for rescue treatment at 24 weeks.
As the plasma MF concentrations of LYR-210 (2500 µg) and LYR-210 (7500 µg) were evaluated at weeks 4, 12, and 24 in the LANTERN study (data on file at Lyra Therapeutics, Inc.), this study aims to characterize the pharmacokinetic profiles of both doses of LYR-210 at earlier timepoints post-placement in patients with CRS.
Twenty-four surgically naïve adult patients with CRS were enrolled in an open-label, multicenter study and underwent in-office bilateral administration of LYR-210 (2500 µg) ( = 12 patients) or LYR-210 (7500 µg) ( = 12 patients) into the middle meatus. Plasma MF concentrations were determined pre-placement and 1-h post-placement (day 1), and on days 2, 3, 7, 14, 21, 28, 42, and 56 by liquid chromatography-tandem mass spectrometry.
Both LYR-210 doses were well-tolerated with no serious adverse events. Systemic MF levels were dose-dependent and lower than reported values of other respiratory MF products. Plasma MF concentrations showed steady drug release from LYR-210 (2500 µg) and LYR-210 (7500 µg) that persisted through day 56.
LYR-210 achieved dose-dependent, continuous local MF delivery at a steady rate with low systemic exposure for months.
由于鼻腔清除迅速和药物向发炎的鼻窦输送不足，局部皮质类固醇在慢性鼻-鼻窦炎（CRS）中的疗效有限。LYR-210 是一种可植入的皮质类固醇基质，旨在通过将糠酸莫米松（MF）局部递送至鼻-鼻窦黏膜，为 CRS 患者提供长达 24 周的治疗。在一项随机、对照、剂量范围的 LANTERN 研究中，LYR-210（7500μg）在 24 周时实现了 CRS 主要症状综合评分、22 项鼻-鼻窦结局测试（SNOT-22）、筛窦混浊和需要抢救治疗的临床相关改善。
由于 LYR-210（2500μg）和 LYR-210（7500μg）的血浆 MF 浓度在 LANTERN 研究中分别在第 4、12 和 24 周进行了评估（Lyra Therapeutics，Inc. 公司文件中提供的数据），本研究旨在描述 CRS 患者放置后更早时间点 LYR-210 两种剂量的药代动力学特征。
24 名接受过手术的 CRS 成年患者参加了一项开放标签、多中心研究，并在办公室内接受双侧 LYR-210（2500μg）（ = 12 名患者）或 LYR-210（7500μg）（ = 12 名患者）的治疗，将药物置于中鼻甲。通过液相色谱-串联质谱法在放置前（第 1 天）和放置后 1 小时（第 1 天）以及第 2、3、7、14、21、28、42 和 56 天测定血浆 MF 浓度。
两种 LYR-210 剂量均耐受良好，无严重不良事件。全身 MF 水平呈剂量依赖性，低于其他呼吸 MF 产品的报告值。LYR-210（2500μg）和 LYR-210（7500μg）的血浆 MF 浓度显示药物持续释放，持续至第 56 天。
LYR-210 实现了剂量依赖性、持续的局部 MF 递送至鼻窦，以稳定的速度输送，全身暴露水平较低，可持续数月。
