In a publication in the October 22, 2020 issue of New England Journal of Medicine, researchers describe results from a phase 2 trial of AK002 (now assigned the generic medication name lirentelimab) in patients with eosinophilic gastritis (EG) and eosinophilic duodenitis (EoD). These conditions are characterized by high counts of eosinophils and mast cells in the stomach and duodenum. Eosinophilic duodenitis (EoD) is a newer and more specific term for eosinophilic gastroenteritis when the first part of the small bowel, the duodenum, is primarily involved (the stomach may or may not be involved at the same time).
Lirentelimab, currently an infusion therapy (delivered through an IV line), is an antibody that targets a receptor known as Siglec-8 and leads to depletion of eosinophils and inhibition of mast cells. Dr. Dellon at University of North Carolina Chapel Hill and Dr. Kathryn Peterson from the University of Utah co-led a team conducting this trial of symptomatic adults with EG, EoD, or both to determine the effectiveness of this potential therapy for these subsets of eosinophilic gastrointestinal disease. The results are promising: Study participants receiving the therapy were shown to have significant decreases of the eosinophil counts in their tissue, as well as substantial symptom improvement compared to those who took placebo.
This study is the first randomized trial for people with EG and EoD, who often struggle with limited, often ineffective treatment options, including corticosteroids, dietary therapy, or a combination of both.
We recently had the opportunity for a brief interview with one of the study’s co-leaders, Dr. Dellon to learn more about this research:
APFED: On average, how long did it take for patients in the trial who were taking AK002 to see relief of symptoms?
Dr. Dellon: In the active treatment arm, symptom improvement compared to placebo was seen as early as 1 week after the initial infusion. After this, there was a continued and sustained decrease in symptoms through the course of the study.
APFED: Did the drug appear to be well-tolerated overall?
Dr. Dellon: Yes, the drug was tolerated well overall. The main thing that was noted more commonly in the active treatment arm was infusion reactions, most of which were mild to moderate, and generally occurred with the first infusion. Efforts are under way to minimize these reactions in the future. There were no other side effects that were more commonly seen in the active compared to the placebo arms.
APFED: What is the impact of this study for patients and for members of the medical community?
Dr. Dellon: One main impact for patients and the medical community is HOPE! This is the first randomized trial to ever be performed in a non-EoE EGID, and the results were so promising that the medication has already moved into phase 3 testing, which is required for drug approval. Another impact is that this study provides the understanding that targeting the Siglec-8 pathway is a good treatment strategy in EG/EoD, and will likely be a good strategy in EoE as well.
A phase-3 study of lirentelimab for EG/EoD is now underway, as well as a phase 2/3 study to evaluate effectiveness of this therapy in eosinophilic esophagitis.
Learn more about clinical trials that are actively enrolling patients, including AK002.
Read related press release from UNC School of Medicine.
References and Resources
Dellon ES, Peterson KA, et. al. “Anti–Siglec-8 Antibody for Eosinophilic Gastritis and Duodenitis”. N Engl J Med 2020; 383:1624-1634, DOI: 10.1056/NEJMoa2012047