BACKGROUND: Eosinophilic gastritis and duodenitis are characterized by 
gastrointestinal mucosal eosinophilia, chronic symptoms, impaired quality of 
life, and a lack of adequate treatments. Mast-cell activity may contribute to 
the pathogenesis of the conditions. AK002 (lirentelimab) is an anti-Siglec-8 
antibody that depletes eosinophils and inhibits mast cells and that has shown 
potential in animal models as a treatment for eosinophilic gastritis and 
duodenitis.
METHODS: In this phase 2 trial, we randomly assigned adults who had symptomatic 
eosinophilic gastritis, eosinophilic duodenitis, or both conditions in a 1:1:1 
ratio to receive four monthly infusions of low-dose AK002, high-dose AK002, or 
placebo. The primary end point was the change in gastrointestinal eosinophil 
count from baseline to 2 weeks after the final dose; to maximize statistical 
power, we evaluated this end point in the placebo group as compared with the 
combined AK002 group. Secondary end points were treatment response (>30% 
reduction in total symptom score and >75% reduction in gastrointestinal 
eosinophil count) and the change in total symptom score.
RESULTS: Of the 65 patients who underwent randomization, 43 were assigned to 
receive AK002 and 22 were assigned to receive placebo. The mean percentage 
change in gastrointestinal eosinophil count was -86% in the combined AK002 
group, as compared with 9% in the placebo group (least-squares mean difference, 
-98 percentage points; 95% confidence interval [CI], -121 to -76; P<0.001). 
Treatment response occurred in 63% of the patients who received AK002 and in 5% 
of the patients who received placebo (difference, 58 percentage points; 95% CI, 
36 to 74; P<0.001). The mean change in total symptom score was -48% with AK002 
and -22% with placebo (least-squares mean difference, -26 percentage points; 95% 
CI, -44 to -9; P = 0.004). Adverse events associated with AK002 were similar to 
those with placebo, with the exception of higher percentages of patients having 
mild-to-moderate infusion-related reactions with AK002 (60% in the combined 
AK002 group and 23% in the placebo group).
CONCLUSIONS: In patients with eosinophilic gastritis or duodenitis, AK002 
reduced gastrointestinal eosinophils and symptoms. Infusion-related reactions 
were more common with AK002 than with placebo. (Funded by Allakos; ENIGMA 
ClinicalTrials.gov number, NCT03496571.).