Phase 1 clinical study to assess the safety of a novel drug delivery system providing long‐term topical steroid therapy for chronic rhinosinusitis

Abstract

Background Chronic rhinosinusitis (CRS) patients who fail medical management have few treatment options other than endoscopic sinus surgery (ESS). A novel biodegradable mometasone furoate drug delivery system (LYR‐210) providing continuous topical steroid therapy to sinonasal mucosa over 24 weeks was developed to treat unoperated CRS patients who have failed medical management prior to ESS. LYR‐210 was designed to slowly expand in the middle meatus, ensuring efficient drug delivery as mucosal swelling reduces. Methods A prospective, multicenter, open‐label study was conducted in 20 CRS subjects who were determined to be candidates for ESS. Under endoscopic guidance and topical anesthesia, LYR‐210 was placed in both middle meatuses. The primary endpoint was product‐related serious adverse events (SAEs) at 4 weeks. Additional assessments included plasma drug concentration, morning serum cortisol levels, intraocular pressures (IOPs), and Sino‐Nasal Outcome Test (SNOT‐22) scores. Results LYR‐210 was successfully placed bilaterally in 20 subjects (12 without nasal polyps and 8 with polyps) in an office setting. There were no product‐related SAEs through 24 weeks, at which point 86% of LYR‐210 depots were still retained in the middle meatus. Serum cortisol, IOP, and plasma drug concentrations supported systemic safety at all time points tested. Subjects experienced significant reductions in their SNOT‐22 scores as early as week 1, and this reduction persisted through week 24 (p < 0.01). Significant symptom improvement was achieved in the SNOT‐22 rhinologic, extranasal rhinologic, ear‐facial, psychological, and sleep dysfunction subdomains at 24 weeks (p < 0.05). Conclusion LYR‐210 is safe and well‐tolerated in ESS‐naive CRS patients and leads to sustained symptom improvement in patients.

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

“…LYR-210 demonstrated a reproducible treatment effect in surgically naive CRS patients regardless of polyp status in 2 different clinical studies. The CFBL on the SNOT-22 over the 24-week treatment period observed for LYR-210 (2500 µg) in the LANTERN Phase 2 study is consistent with that of LYR-210 of the same dose in a phase 1 study, 12 which further validates the findings of the present study.…”

Intraoperative Applications of Topical Corticosteroid Therapy for Chronic Rhinosinusitis

“…Excluded from this review are reports of drug-eluting biomaterials that are intended to be placed in the office setting. These technologies include the Sinuva (Intersect ENT) 41,42 and LYR-210 implants (Lyra Therapeutics), 43 both of which have also shown clinical benefits for patients with CRS. The Sinuva steroid-releasing stent, which is placed into a previously opened ethmoid cavity for recurrent nasal polyposis, has received FDA approval for use since 2017, whereas LYR-210 is currently in phase 2 clinical development for treatment in surgically naive patients with CRS.…”

Topical glucocorticoid treatment for chronic rhinosinusitis in the biologic era

“…However, the patients in this single cohort trial had also undergone sinus surgery and were permitted to use saline irrigations. More recently, a Phase I open‐label, single‐arm study 17 of an alternate mometasone eluting stent design (2500 µg over 24 weeks) was reported with an –16.8‐point to –31.5‐point improvement in SNOT‐22 between weeks 8 to 24 in 20 patients.…”