Fluticasone Propionate Orally Disintegrating Tablets Outperformed Placebo in the Treatment of Eosinophilic Esophagitis

Results of the recently completed FLUTicasone in EoE (FLUTE-2) clinical trial showed that patients with eosinophilic esophagitis (EoE) experienced symptomatic and histologic improvements after being treated with fluticasone propionate orally disintegrating tablets for 12 weeks. Evan S. Dellon, MD, professor of medicine and Director of the Center for Esophageal Diseases and Swallowing at the University of North Carolina, Chapel Hill, who served as the primary investigator for FLUTE-2, discussed the findings during a podium presentation at the Digestive Disease Week 2024 meeting.

Topical steroids have traditionally been used in the treatment of EoE as off-label formulations adapted from asthma preparations. Although EoE-specific formulations of budesonide have been approved for EoE, no formulations of fluticasone targeting EoE are currently available on the market. A novel once daily, orally disintegrating formulation of fluticasone propionate (APT-1011) was designed to deliver the steroid directly to the esophageal mucosa to curb local inflammation, with low systemic absorption.

Patients enrolled in the two-part, double-blind FLUTE-2 trial were randomized to receive APT-1011 (97 patients) or placebo (46 patients). Participants had at least three biopsy samples each from the proximal and distal esophagus, showing a peak count of 15 or more eosinophils per high power field, and at least six self-reported episodes of dysphagia in the 14 days before the start of therapy.

After 12 weeks of treatment, 27% of those who received the fluticasone propionate formulation had complete symptomatic response, defined as no dysphagia episodes over 14 consecutive days, compared to 11% of the participants in the placebo arm. Among symptomatic responders, a vast majority (81%) of patients who received APT-1011 experienced eosinophilic remission. Histologic remission was defined as the presence of 6 or fewer eosinophils per high power field. In contrast, none of the patients in the placebo arm who had a complete symptomatic response experienced histologic remission.

Results from the FLUTE-2 trial also showed that once daily fluticasone propionate orally disintegrating tablets, taken over 12 weeks, outperformed placebo in improving fibrostenotic complications caused by EoE. Of the 143 subjects randomized in the trial, 41 treated with fluticasone propionate and 20 who received placebo had strictures or grade 2/3 rings at baseline. Patients who took APT-1011 had higher rates of stricture resolution and improvement of grade 2/3 rings than those randomized to placebo (59% vs 25.0%). Longer durations of fluticasone propionate therapy, continued during the extension periods up to 38 or 52 weeks, showed similar results, with sustained improvement in most cases.

“Collectively, these outcomes indicate that APT-1011, a topical once-daily fluticasone propionate in an orally disintegrating tablet is a promising therapy for the treatment of EoE symptoms and fibrostenotic complications,” Dellon said.

The speaker noted that fluticasone propionate therapy was generally well tolerated in the study. Adverse events were comparable between the treatment arms, with no reports of adrenal suppression.