Exhalation delivery system with fluticasone passes muster in two chronic rhinosinusitis trials

In the treatment of chronic rhinosinusitis (CRS), exhalation delivery system with fluticasone (EDS-FLU) provides relief from symptoms while reducing intrasinus disease and the incidence of acute exacerbations, regardless of the presence of polyps, as shown in the phase III trials ReOpen1 and ReOpen2.

The EDS-FLU is a drug-device combination that makes use of an "air burst" delivery system during exhalation. It works by helping push the medication deeper into the sinuses. This exhalation delivery system has been shown to be superior to conventional nasal sprays at reaching the upper and back areas of the nasal cavity. [Ann Allergy Asthma Immunol 2022;128:118-128; Drug Deliv Transl Res 2013;3:42-62]

ReOpen1 and ReOpen2

Two previous NAVIGATE trials demonstrated the efficacy of EDS-FLU for treating CRS with nasal polyps. In the current ReOpen1 (n=332, mean age 49.1 years, 42.5 percent women) and ReOpen2 (n=222, mean age 48.4 years, 50.0 percent women) trials, EDS-FLU was evaluated against placebo in adult CRS patients with or without polyps and in those without polyps only, respectively. The patients received EDS-FLU at either 1 or 2 sprays/nostril (186 μg [low dose] or 372 μg [high dose]) or EDS-placebo, administered twice daily for 24 weeks.  [Am J Rhinol Allergy 2019;33:69-82; J Allergy Clin Immunol 2019;143:126-134.e5]

EDS-FLU performed better than EDS-placebo in terms of the coprimary endpoints. During the first 4 weeks of treatment, the composite symptom score (summed congestion, facial pain/pressure, and nasal discharge scores) decreased by 1.58 points for patients in the low-dose group (p<0.001) and by 1.60 points for those in the high-dose group (p<0.001) versus only by 0.62 point for those in the EDS-placebo group in ReOpen1. The corresponding changes in ReOpen2 were −1.54 and −1.74 points versus −0.81 point (p=0.011 and p=0.001, respectively). [J Allergy Clin Immunol Pract 2024;doi:10.1016/j.jaip.2023.12.016]

Furthermore, patients who received EDS-FLU versus EDS-placebo achieved much bigger reductions in sinus opacification (ie, the average of the percentages of opacified volumes in ethmoid and maxillary sinuses by computed tomography scan) over 24 weeks of treatment both in ReOpen1 (least-squares mean change, −5.58 with low dose and −6.20 with high dose vs −1.60; p=0.045 and p=0.018, respectively) and ReOpen2 (least-squares mean change, −7.00 with low dose and −5.14 with high dose vs 1.19; p<0.001 and p=0.009, respectively).

EDS-FLU lowered the incidence of acute exacerbations by between 56 percent and 66 percent compared with EDS-placebo (p=0.001).

Well tolerated

“EDS-FLU was well tolerated, with adverse events similar to those in previous EDS-FLU trials and to those with standard-delivery nasal steroids delivering drug only to anterior/inferior intranasal regions, several of which are sufficiently safe for over-the-counter availability,” according to the investigators. [Rhinology 2020;58: Am J Rhinol Allergy 2019;33:69-82; J Allergy Clin Immunol 2019;143:126-134.e5; Int Forum Allergy Rhinol 2018;8:869-876]

Based on pooled safety data, the most frequent adverse events in EDS-FLU versus EDS-placebo were epistaxis, COVID-19, headache, and nasopharyngitis.

No effect on treatment success

“[T]he ReOpen program evaluated EDS-FLU in patients entering the trials with persistent symptoms despite use of a standard-delivery nasal steroid,” the investigators said.

While ReOpen1 allowed the inclusion of patients with nasal polyps, its findings were similar to those of ReOpen2, which exclusively enrolled patients without nasal polyps. This, according to the investigators, suggested that the presence or absence of polyps did not affect the treatment outcomes for CRS patients receiving EDS-FLU.

“Together, ReOpen1 and ReOpen2 provide the first replicate, controlled trial evidence demonstrating that a medication can produce subjective (symptoms) and objective (sinus opacification) disease improvement, and reduce acute exacerbations, for all patients with CRS, with or without nasal polyps,” the investigators pointed out.

This is particularly important, given that there are no medications specifically approved by the US Food and Drug Administration for treating CRS in patients without nasal polyps, they added.

“EDS-FLU may be particularly valuable for maximizing the benefits of topical treatment for CRS, with or without nasal polyps, before escalating to more invasive or expensive treatment options such as surgery or monoclonal antibodies,” the investigators said.