FLUTICASONE PROPIONATE ORAL DISINTEGRATING TABLET, APT-1011, LEADS TO A GREATER COMPLETE SYMPTOMATIC RESPONSE RATE COMPARED TO PLACEBO IN SUBJECTS WITH EOSINOPHILIC ESOPHAGITIS (EOE)

Background
The goals of treatment of eosinophilic esophagitis (EoE) are to improve clinical symptoms and histologic features, as well as prevent progression to fibrostenotic complications. Few data currently exist that evaluate the effectiveness of therapies as measured by complete resolution of symptoms. APT-1011, a novel oral disintegrating tablet of fluticasone propionate, a potent glucocorticoid with <1% bioavailability, was designed to target the esophageal mucosa for broad anti-inflammatory effects for the treatment of EoE.

Aim
To evaluate the effect of APT-1011 treatment as measured by complete resolution of symptoms, defined as zero dysphagia-days over 14-consecutive days prior to Week 12, and to assess the relationship of complete symptom resolution with eosinophilic remission (≤6 eosinophils per high power field).

Methods
The FLUTicasone in EoE (FLUTE-2) trial was a 2-Part randomized, double-blind, placebo-controlled study of APT-1011 in adults with EoE. This abstract focuses on Part A in which subjects were randomized to 3 mg APT-1011 or placebo at bedtime for 12 weeks, at which time outcomes were assessed. Dysphagia was measured via an electronic diary daily. All subjects had at least 4 dysphagia days over 14 consecutive days at baseline. Post-hoc analyses were conducted to assess treatment benefit by evaluating complete symptom responders at Week 12, and the percentage of symptomatic responders with concomitant eosinophilic remission on esophageal biopsy.
Results
A total of 143 subjects were randomized (97 APT-1011; 46 placebo) into Part A. The baseline characteristics in each treatment arm were similar (e.g., mean age 41.4 vs. 43.6 years; 58.8% vs. 67.4% male; 90.7% vs. 97.8% White; mean number of dysphagia days over 14 days: 9.7 vs. 9.8, respectively). At Week 12, 26 subjects on APT-1011 (27%) vs. 5 (11%) on placebo had a complete symptom response (p=0.031) (Table 1). Within the cohorts of symptomatic responders, concomitant eosinophilic remission was seen in most subjects in the APT-1011 arm (81%) and in none of the subjects on placebo (Table 2).

Conclusions
As compared to placebo, APT-1011 led to more frequent complete symptom response, the most stringent and clinically meaningful criteria to assess symptomatic benefit, in this post-hoc analysis. Amongst subjects with complete symptom response, eosinophilic remission was only seen in those receiving APT-1011. These data indicate that the depth of symptom resolution with APT-1011 therapy corresponds with eosinophilic remission, making APT-1011 a promising therapy for these important treatment goals.