Annual Scientific Meeting
Evan Dellon, MD, MPH, FACG
Professor of Medicine and Associate Professor of Epidemiology, Center for Esophageal Diseases and Swallowing
University of North Carolina at Chapel Hill School of Medicine
Chapel Hill, NC, US
NO DISCLOSURE INFORMATION SUBMITTED
Introduction: Eosinophilic gastrointestinal (GI) disorders (EGIDs) such as eosinophilic gastritis (EG) and gastroenteritis (EGE), are caused by accumulation and activation of eosinophils (eos) and mast cells (MC), resulting in chronic debilitating symptoms (e.g. abdominal pain, nausea, diarrhea, bloating, abdominal cramping, early satiety, and vomiting). There is no FDA approved treatment for EGIDs and current treatment options are limited. AK002, an anti-siglec-8 antibody, depletes eos and inhibits MC activity, providing a novel targeted therapy for EGID patients. We aimed to assess the efficacy and safety of AK002 in adult patients with EG/EGE.
Methods: ENIGMA was a randomized, double-blind, placebo-controlled phase 2 clinical trial. Biopsy-confirmed EG/EGE patients with moderate to severe symptoms were randomized to AK002 (low dose 0.3-1.0 mg/kg [LD] or high dose 0.3-3.0 mg/kg [HD]) or placebo (PBO) cohorts. Symptoms were assessed using a validated, proprietary, daily EG/EGE questionnaire to generate a total symptom score (TSS). The primary endpoint was mean percent change in GI tissue eos counts from baseline (BL). Secondary endpoints were the proportion of treatment responders (defined as patients with both >75% decrease in tissue eos and >30% improvement in TSS), and mean percent change in TSS from BL. IRB approval was obtained.
Results: 59 patients were evaluable for efficacy (n=20 in HD; n=19 in LD; n= 20 in PBO). BL characteristics were balanced between groups (Table 1). For the primary endpoint, the AK002 groups had an overall 95% mean reduction of tissue eos relative to BL compared to a 10% mean increase in PBO (p<0.0001). Tissue eos depletion to ≤6 eos/hpf was seen in 37 (95%) AK002 patients. There was significant improvement in TSS scores with AK002 compared to PBO (p=0.0012; Table 2). Among all AK002 patients, 69% were treatment responders compared to 5% of PBO patients (p=0.0008). The most common adverse events (AE) reported for AK002 were mild to moderate infusion related reactions (IRR), most common at the first infusion only. Treatment emergent serious AEs were similar between AK002 and PBO groups. There was one drug related SAE, an IRR that resolved within 24 hours without sequelae.
Discussion: In the first RCT in EG/EGE patients, AK002 treatment resulted in depletion of GI tissue eos and significant improvement of EG/EGE symptoms compared to PBO. AK002 was also well tolerated and is a promising candidate for targeted treatment of EGIDs.