ENIGMA Study: Novel Antibody Appears Safe, Effective for Eosinophilic GI Disorders

AK002—an anti-SIGLEC8 antibody—may be a safe and effective treatment option in eosinophilic gastritis (EG) and eosinophilic gastroenteritis (EGE), according to results of ENIGMA, a phase 2 clinical trial. The findings were presented at the American College of Gastroenterology (ACG) 2019 Annual Scientific Meeting and Postgraduate Course.

No treatment has been approved by the US Food and Drug Administration for patients with eosinophilic gastrointestinal (GI) disorders, and treatment options are limited. AK002—which depletes eosinophils (eos) and inhibits mast cell activity—is believed to be a potential novel targeted therapy for persons with eosinophilic GI disorders.

To assess the antibody’s safety and efficacy in adult patients with EG and/or EGE, study coauthor Evan Dellon, MD, MPH, from the University of North Carolina at Chapel Hill School of Medicine, and colleagues, conducted the first randomized controlled trial in patients with biopsy-confirmed EG and/or EGE.

The researchers randomly assigned participants—all of whom had moderate to severe symptoms—to receive a low dose of AK002 (0.3-1.0 mg/kg), a high dose of AK002 (0.3-3.0 mg/kg), or a placebo. The researchers evaluated the efficacy of AK002 from data on 19 participants from the low-dose AK002 group, 20 participants from the high-dose AK002 group, and 20 participants from the placebo group.

The researchers measured the mean percent change in GI tissue eos counts from baseline. Baseline characteristics were balanced between the groups.

From baseline, the two AK002 groups experienced an overall 95% mean reduction in tissue eos count. The participants in the placebo group experienced a 10% mean increase in tissue eos count from baseline.

Among the AK002 groups, 37 participants (95%) had a tissue eos depletion to 6 eos per high-power field or less.

The researchers administered a daily EG/EGE questionnaire to calculate the participants’ total symptom score. Participants who received AK002 had significant improvement in these scores compared with participants who received placebo.

In all, 69% of those in the AK002 groups and 5% of those in the placebo group were treatment responders, which was defined as experiencing more than a 75% decrease in tissue eos and having more than a 30% improvement in total symptom score.

Among the AK002 groups, the most commonly reported adverse events (AEs) were mild to moderate infusion-related reactions, which were most common at the first infusion only. Treatment-emergent serious AEs were similar among all groups.

“In the first [randomized controlled trial] in EG/EGE patients, AK002 treatment resulted in depletion of GI tissue eos and significant improvement of EG/EGE symptoms compared to [placebo],” Dr Dellon concluded. “AK002 was also well tolerated and is a promising candidate for targeted treatment of [eosinophilic GI disorders].” —Colleen Murphy