Fluticasone Propionate (XHANCE) Receives FDA Approval for Chronic Rhinosinusitis

The US Food and Drug Administration has approved fluticasone propionate nasal spray (XHANCE) for the treatment of chronic rhinosinusitis without nasal polyps.

Announced by Optinose on March 15, 2024, the indication is for the treatment of chronic rhinosinusitis without nasal polyps in patients 18 years of age and older and makes fluticasone propionate nasal spray the first and only therapy to receive this indication. The decision comes more than a year after Optinose announced the submission of a supplemental new drug application (sNDA) for fluticasone propionate nasal spray in chronic rhinosinusitis and is based on data from a pair of trials within the phase 3 ReOpen program.^1,2

“The FDA approval of XHANCE for the treatment of CRS without nasal polyps is an important milestone,” said Rick Chandra, M.D., Professor of Otolaryngology-Head and Neck Surgery, Endowed Director, Roland “Ron” Eavey, MD, SM Endowed Directorship in Leadership and Education, Service Chief, Rhinology and Skull Base Surgery, Vanderbilt University. “Until today, we have been forced to use unproven therapies to try and alleviate the symptoms that these patients suffer. While we often resort to using nasal steroid sprays in this patient population, they have never been shown to be effective in large placebo-controlled clinical studies. XHANCE, which uses the Exhalation Delivery System to enable delivery of an established topical steroid to the areas of the nasal cavity and sinuses we know to be extensively inflamed, is now proven to be effective in treating our CRS patients both with and without nasal polyps.”

A topical nasal corticosteroid delivered via Optinose’s Exhalation Delivery System™, fluticasone propionate nasal spray boasts a previous approval for the treatment of nasal polyps in patients 18 years and older dating back to 2017. The road to the March 15, 2024 decision was not straightforward. Optinose announced the submission of their sNDA for the expanded indication on February 21, 2023 and, on December 06, 2023, the company announced the FDA had extended the review period by 3 months.^3,4

According to the December 2023 announcement from Optinose, the FDA contacted the company and request additional efficacy subset analyses of existing clinical data from ReOpen1 related to patients without nasal polyps plus those patients with a nasal polyp grade of one or less at trial entry. The FDA deemed the submission of additional data as a major amendment and extended the PDUFA goal date to Mach 16, 2024.^3,4

ReOpen1 and ReOpen2

Billed as the first placebo-controlled evidence demonstrating efficacy of any medication in chronic rhinosinusitis, the ReOpen1 and ReOpen2 trials were multicenter, randomized, controlled trials comparing use of fluticasone propionate nasal spray against placebo therapy at 120 sites across 13 countries. ReOpen1 included adults with chronic rhinosinusitis irrespective of polyps while ReOpen2 only contained adults with chronic rhinosinusitis without nasal polyps.^5,6

In both trials, patients were randomized to fluticasone propionate nasal spray at 1 or 2 sprays per nostril or placebo delivered via the Exhalation Delivery System twice daily for 24 weeks. In total, 332 patients were randomized in ReOpen1 and 223 were randomized in ReOpen2. Both trials used the same coprimary outcomes of interest, which was a composite symptom score through week 4 and ethmoid/maxillary sinus percent opacification by computed tomography at week 24.⁶

In ReOpen1, the composite symptom score least-squares mean change for fluticasone propionate nasal spray 1 or 2 sprays per nostril was -1.58 and -1.60, respectively, compared to -0.62 with placebo (P for both < .001). In ReOpen2, the composite least-squares mean change for fluticasone propionate nasal spray 1 or 2 sprays was -1.54 and -1.74, respectively, compared to -0.81 with placebo (P for both=.011).⁶

Additional analysis of secondary endpoints in the trials revealed acute disease exacerbations were reduced by 56% to 66% with fluticasone propionate nasal spray relative to placebo (P=.001) and significant symptom reductions were observed among patients, regardless of nasal steroid product use prior to study entry (P < .001).⁶

“Although chronic sinusitis is one of the most common diagnoses in outpatient physician visits, and surgery is available, there has never been a prescription medication approved by the FDA as safe and effective to treat the millions of patients without nasal polyps suffering from this debilitating disease. We are thrilled to now be able to offer new hope to these patients and believe XHANCE has the potential to become part of the standard of care for the treatment of chronic sinusitis.”

References:

1. Optinose. XHANCE approved by FDA as first and only medication indicated for treatment of adults with chronic rhinosinusitis without nasal polyps. Optinose. Accessed March 15, 2024. https://ir.optinose.com/news-releases/news-release-details/xhance-approved-fda-first-and-only-medication-indicated.
2. Optinose. Optinose submits Supplemental New Drug Application for XHANCE label expansion. Optinose. February 21, 2023. Accessed March 15, 2024. https://ir.optinose.com/news-releases/news-release-details/optinose-submits-supplemental-new-drug-application-xhance-label.
3. BioSpace. Optinose announces FDA approval of XHANCE (fluticasone propionate) nasal spray for the treatment of nasal polyps. BioSpace. September 19, 2017. Accessed March 15, 2024. https://www.biospace.com/article/releases/optinose-announces-fda-approval-of-xhance-fluticasone-propionate-nasal-spray-for-the-treatment-of-nasal-polyps-/.
4. Optinose. Optinose announces 3-month extension of FDA review period for the Supplemental New Drug Application for XHANCE. Optinose. December 6, 2023. Accessed March 15, 2024. https://ir.optinose.com/news-releases/news-release-details/optinose-announces-3-month-extension-fda-review-period.
5. Optinose. Optinose announces the publication of reopen phase 3 clinical trial program evaluating XHANCE in the Journal of Allergy and Clinical Immunology: In Practice. Optinose. January 18, 2024. Accessed March 15, 2024. https://ir.optinose.com/news-releases/news-release-details/optinose-announces-publication-reopen-phase-3-clinical-trial.
6. Palmer JN, Adappa ND, Chandra RK, et al. Efficacy of EDS-FLU for Chronic Rhinosinusitis: Two Randomized Controlled Trials (ReOpen1 and ReOpen2). J Allergy Clin Immunol Pract. Published online January 5, 2024. doi:10.1016/j.jaip.2023.12.016