NAVIGATE II: Randomized, double-blind trial of the exhalation delivery system with fluticasone for nasal polyposis

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.

Section: Discussionsupporting

confidence: 68%

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

Douglas

Psaltis

Rimmer

et al. 2019

“…EDS‐FLU is a new treatment with potential to improve medical care of CRS in patients who do not respond satisfactorily to conventional nasal steroids by enabling reliable and consistent outpatient delivery of steroid to high and deep target sites of inflammation . In addition, studies have suggested the possibility that direct EDS device benefits could be produced by the effects of carbon dioxide in exhaled breath (influencing inflammatory mediator and neuropeptide activity), by removal of nitric oxide, by positive pressure, or by change in pH .…”

Section: Discussionmentioning

confidence: 99%

“…Two large, randomized controlled trials were performed to establish the efficacy of EDS‐FLU in patients with CRSwNP . However, practical data that more closely resemble “real‐world evidence” for the benefits of long‐term treatment are also valuable.…”

Section: Discussionmentioning

confidence: 99%

EXHANCE‐12: 1‐year study of the exhalation delivery system with fluticasone (EDS‐FLU) in chronic rhinosinusitis

Palmer

Jacobson

Messina

et al. 2018

Self Cite

BackgroundInadequate efficacy of current intranasal steroids in chronic rhinosinusitis (CRS) is attributable to ineffective and/or inconsistent drug delivery to target anatomic sites. A new exhalation delivery system with fluticasone (EDS‐FLU) may improve outcomes by significantly increasing superior/posterior corticosteroid delivery. A study was conducted to assess the long‐term efficacy and safety outcomes of EDS‐FLU in individuals with CRS.MethodsThis was a 12‐month, multicenter, single‐arm study evaluating the safety and efficacy of EDS‐FLU 372 μg twice daily in CRS patients (with [n = 34] or without [n = 189] nasal polyps [NP]). Efficacy assessments by serial nasal endoscopy and patient report included: 22‐item Sino‐Nasal Outcome Test (SNOT‐22), NP grade, standardized surgical indicator assessment, Lund‐Kennedy score, and Patient Global Impression of Change. Adverse event (AE) evaluations included nasal endoscopy. Additional safety and efficacy outcomes were assessed.ResultsOf 223 patients who received EDS‐FLU, 96% reported prior corticosteroid use and 29% prior sinus surgery. The EDS‐FLU AE profile was similar to conventional intranasal steroids studied in similar populations. Most patients (87%) reported symptom improvement. Through 12 months, mean SNOT‐22 scores improved by −21.5 and −21.1 for CRS with and without NP, respectively. Among patients with NP, 54.2% had polyp elimination in at least 1 nostril and 83.3% had ≥1‐point improvement in polyp grade.ConclusionOver 1 year of treatment in CRS with and without NP, EDS‐FLU 372 μg twice daily was well tolerated and produced improvements across a broad range of objective and subjective measures. EDS‐FLU may be a desirable new option for patients with this condition.

“…The remainder of the articles were excluded as they focused on fluticasone use in lower airway disease (n = 129), were centered on exhaled gas measurements for the evaluation and monitoring of lower airway disease (n = 67), or discussed use of the EDS in migraine therapy (n = 4). The majority of the evidence surrounding the efficacy of EDS‐FLU is from 4 large‐scale studies that were performed as part of the FDA‐approval process, namely EXHANCE‐3, EXHANCE‐12, NAVIGATE I, and NAVIGATE II . The relevant data and outcomes these trials are summarized in what follows (Table ).…”

Section: Resultsmentioning

confidence: 99%

Efficacy of fluticasone exhalation delivery system in the management of chronic rhinosinusitis: what is the evidence?

Kuan

Kovacs

Workman

et al. 2019

Background: Intranasal steroids have become part of the mainstay in the long-term management of chronic rhinosinusitis. A long-standing problem remains in efficient and easy-to-use delivery of topical corticosteroids to the nasal mucosa. Currently available means of intranasal steroid delivery include sprays, which are generally limited to treating the anterior nasal cavity, and rinses, which are not FDA-approved for this indication. The exhalation delivery system is a novel method of delivering fluticasone to the deeper areas within the nasal cavities, including the posterior nasal cavity and middle and superior meatuses. Methods: Comprehensive literature review. Results:Recent large scale studies have suggested its efficacy and safety in the use of patients with both chronic sinusitis with polyposis and without polyps. Specifically, studies have demonstrated decreased Sinonasal Outcome Test scores of 20 points following treatment, as well as improvement of polyp grade by 1 or more point in more than 60% of patients. Furthermore, among patients with nasal polyps, there was approximately 60-70% decreased indication for surgery following EDS-FLU use.