Lirentelimab efficaciously and safely reduced histologic disease activity in most patients, but especially adolescents, with eosinophilic esophagitis (EoE), according to study results presented at the American College of Gastroenterology (ACG) 2022 Annual Meeting, held from October 21 to 26, 2022, in Charlotte, North Carolina, and virtually.
Researchers conducted a randomized, double-blind, placebo-controlled, phase 2/3, clinical trial (KRYPTOS; ClinicalTrials.gov Identifier: NCT04322708) to assess the safety and efficacy of lirentelimab in the treatment of adults and adolescents with EoE. In this clinical trial, 51 of the 276 participating patients were adolescents between the ages of 12 and 17.
Researchers randomly assigned patients diagnosed with EoE who had symptoms of dysphagia and at least 15 eosinophils per high-power field (eos/hpf) on esophageal biopsy into 3 groups.
The first group (n=92) received high-dose lirentelimab (1 mg/kg per 1 dose followed by 3 mg/kg per 5 doses) for 24 weeks. The second group (n=92) received low-dose lirentelimab (1 mg/kg), while the placebo group received 6 monthly infusions during the 24-week study.
The coprimary endpoints were for patients to achieve histologic response (peak eos count of ≤6 eos/hpf at 24 weeks) and mean absolute change in score from baseline to weeks 23 to 24 per a daily Dysphagia Symptom Questionnaire.
By week 24, 88% of the high-dose and 92% of the low-dose treatment groups had achieved the histologic endpoint, compared with 11% in the placebo group (P <.0001).
When analyzing the adult and adolescent subgroups separately, 94% of adolescents in each of the high- and low-dose groups achieved the histologic endpoint, compared with 6% in the placebo group.
The average absolute change in DSQ scores from baseline to week 24 showed a 17.4-point reduction in the high-dose group and a 11.9-point reduction in the low-dose group, compared with a 14.6-point reduction in the placebo group (P =.2372). Adolescents in the high- and low-dose groups on average scored 18.4 and 16.4 points lower on the DSQ, respectively, compared with adolescents in the placebo group, who scored 8.9 points lower (P =.1316).
Only 3 serious adverse events occurred (2 in the high-dose group and 1 in the placebo), but most adverse events were infusion-related reactions (38.5%, 25.8%, and 12% in the high-dose, low-dose, and placebo groups, respectively) and headache (6.6%, 8.6%, and 6.5% in the high-dose, low-dose, and placebo groups, respectively).
“This phase 2/3 trial of lirentelimab met the histologic co-primary endpoint but did not meet the DSQ symptom co-primary endpoint, although in adolescents there was a trend in DSQ response over PBO,” the study authors wrote.
Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
Dellon E, Chehade M, Genta RM, et al. Results from KRYPTOS, a phase 2/3 study of lirentelimab (AK002) in adults and adolescents with EoE. Abstract presented at: ACG 2022 Annual Meeting; October 21-26, 2022; Charlotte, NC. Abstract D0201.