Clinical Trial: Safety and Efficacy of a Novel Oesophageal Delivery System for Topical Corticosteroids Versus Placebo in the Treatment of Eosinophilic Oesophagitis

ABSTRACT

Background

EsoCap is a thin mucoadhesive film designed to target the oesophageal mucosa. The device loaded with mometasone furoate (ESO-101) is under investigation for the treatment of eosinophilic oesophagitis (EoE).

Aims

To evaluate the efficacy, safety and tolerability of ESO-101 in patients with active EoE.

Methods

We conducted a randomised, placebo-controlled, phase 2, proof-of-concept trial at 14 European sites in adults with EoE. Participants received placebo, uncoated EsoCap (n = 15), or EsoCap loaded with 800 μg of mometasone furoate (n = 28) once daily during 28 days. The primary outcome was the absolute change in the peak eosinophil count; secondary outcomes were histologic, clinical and endoscopic measures.

Results

Treatment with ESO-101 resulted in reduction (mean ± SD) of 49.1 ± 88.4 eosinophils/high-power field from baseline, compared with 6.6 ± 65.1 with placebo (p = 0.03). With ESO-101, 48% and 44% of patients achieved < 15 and < 6 eosinophils/high-power field, respectively; these were 0% with placebo. EoE Endoscopic Reference Score reduced significantly in patients treated with ESO-101. In contrast, dysphagia and odynophagia severity decreased similarly in both groups. There were no serious treatment-emergent adverse events. Mean serum cortisol did not change significantly throughout the trial. Notably, no oropharyngeal or oesophageal candidiasis was documented. The device was well tolerated.

Conclusions

ESO-101 was superior to placebo in reducing oesophageal eosinophilia. The device was safe and well tolerated in adults with EoE, supporting the continued development of ESO-101 for the treatment of EoE (Trials.gov No.: NCT04849390; Eu-CT No.: 2020–000082-16).

Introduction

Eosinophilic oesophagitis (EoE) is a chronic inflammatory disease of the oesophagus, characterised by eosinophilic infiltration and upper gastrointestinal symptoms [1, 2]. Standard-of-care treatments for EoE include food elimination diets [3], proton-pump inhibitors (PPIs) [4] and swallowed topical corticosteroids [5]. Recently, a new biological treatment directed against the interleukin-4 receptor alpha has been added to the therapeutic armamentarium for EoE [6]. Oesophageal dilatation is also performed in the case of strictures [7]. The goal of topical therapy with corticosteroids in EoE is to maximise loco-regional efficacy with oesophageal-specific drug delivery and drug formulation, while reducing systemic bioavailability and thus avoiding systemic effects [1]. However, topical corticosteroid therapy in EoE has yielded widely heterogeneous results due the use of different active ingredients and doses, administration methods, formula composition and different volumes [8]. To date, topical forms of budesonide have been approved for EoE [9-12], and historically fluticasone was also used, albeit frequently delivered from an asthma inhaler [10]. In addition, the available data and pharmacological features of mometasone furoate, a different corticosteroid, are promising regarding efficacy in EoE [13-15].

ESO-101 is an innovative, unique pharmaceutical in the form of a thin mucoadhesive film containing mometasone furoate, designed for targeted oesophageal administration of the active substance in the oesophagus [16]. The film enables a long mucosal contact time and maximises the deposition of mometasone furoate, a key goal in EoE. Importantly, the ESO-101 film has no contact with the oral mucosa, but rather delivers the corticosteroid directly to the oesophageal mucosa. Because of minimal enteral absorption of mometasone furoate and because the portion of the mometasone furoate dose absorbed in the gastrointestinal tract undergoes extensive hepatic metabolism, systemic bioavailability is low [17], suggesting the possible of a low rate of systemic side effects [18].

Nevertheless, ESO-101 needed to be tested clinically to demonstrate proof-of-concept. Therefore, the aim of this double-blind, randomised, placebo-controlled trial was to investigate the efficacy, safety and tolerability of mometasone furoate administered via the ESO-101 delivery system.

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Luisa Bertin, Edoardo Vincenzo Savarino, Editorial: Targeting the Future of Eosinophilic Oesophagitis Management, Alimentary Pharmacology & TherapeuticsAlimentary Pharmacology & TherapeuticsAlimentary Pharmacology & Therapeutics, 10.1111/apt.18449.