Long-acting implantable corticosteroid matrix for chronic rhinosinusitis: Results of LANTERN Phase 2 randomized controlled study

Abstract

Background: Topical steroids are first-line treatment for chronic rhinosinusitis (CRS), but fail to provide adequate symptom control for all patients. Designed for medical treatment failures, LYR-210 is an implantable matrix that locally elutes mometasone furoate to inflamed sinonasal tissue for up to 24 weeks in CRS patients. In an open-label phase 1 study, LYR-210 demonstrated clinically relevant improvement in the 22-item Sino-Nasal Outcome Test (SNOT-22). Safety and efficacy of LYR-210 in CRS were evaluated in the LANTERN Phase 2 study.

Methods: Sixty-seven surgically naive adult CRS patients who were inadequately controlled by previous medical management and seeking an alternative treatment enrolled in a multicenter, blinded, controlled, dose-ranging study. Patients had moderate-to-severe disease based on SNOT-22 and composite 7-day average scores of the 4 cardinal CRS symptoms (4CS), with diagnosis confirmed by nasal endoscopy and magnetic resonance imaging. Patients were randomized (1:1:1) to saline irrigation-only control or bilateral in-office administration of LYR-210 (2500 μg) or LYR-210 (7500 μg). Safety and efficacy were evaluated over 24 weeks.

Results: Both LYR-210 doses were safe and well-tolerated over the 24-week treatment period. LYR-210 demonstrated rapid and durable dose-dependent symptom improvement based on 4CS and SNOT-22, with LYR-210 (7500 μg) achieving statistical significance as early as 8 weeks and out to 24 weeks compared with control. LYR-210 (7500 μg) reduced rescue treatment use and radiographic ethmoid opacification at week 24.

Conclusions: LYR-210 is the first implantable sinonasal treatment to achieve up to 24 weeks of benefit from a single administration in surgically naive CRS patients with and without nasal polyps.

Keywords: chronic sinusitis; local drug delivery; mometasone furoate; nasal polyps; sinus procedure; surgically naive.

© 2021 The Authors. International Forum of Allergy & Rhinology published by Wiley Periodicals LLC on behalf of American Academy of Otolaryngic Allergy and American Rhinologic Society.

Figures

FIGURE 1

LYR‐210 matrix self‐expands from a constrained state when deployed from an applicator.

FIGURE 2

LANTERN Phase 2 study design schematic.

FIGURE 3

Disposition of patients (CONSORT) diagram. ITT = intention to treat.

FIGURE 4

Patient symptom improvement in nasal blockage, facial pain/pressure, and nasal discharge. Mean change from baseline (CFBL) in the 7‐day average score in (A) nasal blockage, (B) facial pain/pressure, and (C) nasal discharge (anterior/posterior). Data are presented as LSM. p < 0.05 considered statistically significant compared with control.

FIGURE 5

Patient‐reported loss‐of‐smell scores in patients with moderate‐to‐severe baseline anosmia. Mean change from baseline (CFBL) in the 7‐day average score in loss of smell for patients with moderate‐to‐severe baseline anosmia (≥2 baseline score in loss of sense of smell). Patients per group: LYR‐210 (7500 μg), n= 15; LYR‐210 (2500 μg), n = 20; and control, n = 20. Data are presented as LSM.

FIGURE 6

Patient symptom improvement as measured by composite score of (A) 4 cardinal symptoms (4CS) and (B) 3 cardinal symptoms (3CS). Mean changes from baseline (CFBL) in 7‐day average score in 4CS include nasal blockage, facial pain/pressure, nasal discharge (anterior/posterior), and loss of smell. For 3CS, these include nasal blockage, facial pain/pressure, and nasal discharge (anterior/posterior). Data are presented as LSM. p < 0.05 considered statistically significant compared with control.

FIGURE 7

Patient symptom improvement as measured by SNOT‐22. (A) Mean change from baseline (CFBL) in SNOT‐22 total score. Data presented as LSM. p < 0.05 considered statistically significant compared with control. (B) Percentages of patients administered bilateral LYR‐210 (2500 μg), bilateral LYR‐210 (7500 μg), or control who achieved minimal clinically important difference (MCID) in SNOT‐22 total score at week 24. (C) Percentages of patients with nasal polyps vs without nasal polyps administered bilateral LYR‐210 (2500 μg), bilateral LYR‐210 (7500 μg), or control who achieved MCID in SNOT‐22 total score at week 24.

FIGURE 8

Reduction in ethmoid sinus opacification as measured by bilateral Zinreich MRI scores. Mean change from baseline (CFBL) in the bilateral ethmoid Zinreich score (composite score of anterior ethmoid and posterior ethmoid Zinreich scores) at 24 weeks. Data are presented as means. p < 0.05 considered statistically significant compared with control.

FIGURE 9

Time to first rescue treatment use over 24 weeks. An event is when rescue treatment was used. Patients who did not achieve the event were censored at the end of treatment date or at the early termination date. Use of rescue treatment over the 24‐week treatment period was as follows: LYR‐210 (7500 μg), 1 patient; LYR‐210 (2500 μg), 2 patients; and saline irrigation control, 7 patients.