26 (S0345). - Safety and Efficacy of Long-Term Treatment of EoE With Fluticasone Propionate Orally Disintegrating Tablet (APT-1011): Results From 40 Weeks Treatment in a Phase 2b Randomized Double-Blind Placebo-Controlled Trial
Evan S. Dellon, MD, MPH1, Alfredo Lucendo, MD, PhD, FEBGH2, Christoph Schlag, MD3, Alain Schoepher, MD4, Gary W. Falk, MD, FACG5, Peter Richardson, MD6, Gina Eagle, MD6, James Nezamis, MS6, Gail Comer, MD6, Karol Knoop, RN, BS, CCRA6, Ikuo Hirano, MD7; 1University of North Carolina at Chapel Hill, Chapel Hill, NC; 2Head of the Department of Gastroenterology, Tomelloso, Madrid, Spain; 3II. Medizinische Klinik Klinikum rechts der Isar, Technical University Hospital, Munchen, Bayern, Germany; 4FMH Médecine Interne FMH Gastroentérologie et Hépatologie, Lausanne, Vaud, Switzerland; 5University of Pennsylvania Perelman School of Medicine, Philadelphia, PA; 6Adare Pharma, Lawrence Township, NJ; 7Northwestern University Feinberg School of Medicine, Chicago, IL
Introduction: APT-1011, a novel fluticasone propionate orally disintegrating tablet, induced histological remission and symptom improvement in adults with eosinophilic esophagitis (EoE) after 12 weeks in a phase 2b study. We aimed to evaluate long-term safety and efficacy of APT-1011 in maintaining remission for 52 weeks. Methods: The FLUTE trial was a 2-part randomized, double-blind, placebo-controlled, dose-ranging study of APT-1011 vs placebo. Participants from 71 sites in 6 countries (N. America; Europe) were randomized in Part 1 to APT-1011 (1.5 mg HS or BID; 3 mg HS or BID) or placebo for 12 weeks. In Part 2, histological responders (≤6 eos/HPF) at Week 12 continued the same treatment to Week 52, and non-responders were assigned to 3 mg BID to Week 52. Histologic remission was evaluated at Weeks 26 and 52. Additional endpoints included endoscopic activity, symptoms and safety. Results: Of 97 subjects who completed Part 1, 93 entered Part 2. Responder rates in Part 1 were 80% 3 mg BID; 67% 3 mg HS; 86% 1.5 mg BID; 48% 1.5 mg HS and 0% placebo. For APT-1011 responders at Week 12, daily doses of 3 mg and 6 mg resulted in sustained remission rates (64-84%) compared to 1.5 mg daily (30%) (Table 1). Of participants on placebo in Part 1, 80% had histological remission at Week 26 with 67% maintaining remission at Week 52. Of APT-1011 non-responders in Part 1, 26% achieved histological remission with ongoing treatment (3 mg BID) at Week 52 (Table 2). For APT-1011 responders in Part 1, the reduction in the number of dysphagia episodes at Week 12 was maintained or further reduced in Part 2; global EoE symptom scores continued to improve for the 3 mg BID and 3 mg HS groups; endoscopic improvement (EREFs) continued for all APT-1011 groups (Figure 1). The most common adverse events were oral/esophageal candidiasis in 11/93 (12%), the majority with BID dosing (7/11 3 mg BID; 3/11 1.5 mg BID; 1/11 3 mg HS). Two abnormal ACTH tests were reported at Week 52; one associated with 19-nortestosterone use and another with lab draw at the incorrect time. Discussion: APT-1011 is highly efficacious for treatment and maintenance of histologic remission in adults with EoE over 52 weeks. The 3 mg HS dose demonstrated the best benefit/risk balance of efficacy and safety, for both induction and maintenance of remission over 52 weeks, with the added benefit of once daily dosing. In addition, one out of 4 APT-1011 treatment failures in Part 1of this study, responded to continued high dose APT-1011.
Maintenance of Histological Response Analysis at Weeks 26 and 52 in Week 12 Responders
Histological Response at Week 26 and Maintenance of Response at Week 52 Analysis in Week 12 Non-responders
Dysphagia Episodes, Global EoE Symptom Scores and EREF Scores over Time by APT-1011 Dosing Group