D2.183 - Assessment of Incidence and Onset of Eosinophilic Esophagitis during the clinical development of Peanut (Arachis hypogaea) Allergen Powder-dried non-fat protein for oral immunotherapy

Eosinophilic Esophagitis (EoE) is a chronic, immune-mediated condition that has gained increasing recognition over the past three decades, particularly among children with IgE-mediated food allergies, where its prevalence (4,7%) is higher than in the general population (0,04%). The emergence of EoE has been reported during oral immunotherapy (OIT) for various food allergies. A systematic review estimated the incidence of new-onset EoE in OIT-treated individuals to be as high as 2,7% (95% CI: 1,7%–4,0%). In this study, we evaluate the incidence and timing of EoE onset during the clinical development of Peanut (Arachis hypogaea) Allergen Powder- dried non-fat protein (PDAH) for OIT in patients with peanut allergy.

PDAH was evaluated in nine clinical trials (including three open-label extension studies). At data cut-off (7 June 2024), 1375 participants had been followed out to a maximum of over 10 years (including parent studies). Biopsy-confirmed cases of EoE were reviewed.

Across the entire development program, 17 cases of biopsy-confirmed EoE were reported among the 1375 participants (1,2%) who received at least one dose of PDAH. Investigators classified 16 of 17 cases as treatment-related. For six cases, the first symptoms occurred during the up-dosing phase, while the remaining cases emerged during the maintenance phase (300 mg peanut protein), with a median onset around 471 days (range: 20-1856 days) after treatment initiation.

Among the patients with EoE, the majority were male (n=12/16; 75,0%) and children (15/16), with only one case occurring in an adult (a 33-year-old female). No cases of EoE were reported in participants who started treatment before the age of 3. Following product discontinuation, 75% experienced symptomatic improvement.

While clinical vigilance remains essential, we report a 1,2% incidence rate of biopsy-confirmed and treatment related Eosinophilic Esophagitis (EoE) (16/1375) among participants treated with Peanut (Arachis hypogaea) Allergen Powder-dnfp (PDAH) during the clinical development program, with no cases occurring in the toddler age group. Given current literature, these findings suggest that OIT with PDAH does not present a higher risk of EoE compared to other forms of oral immunotherapy.