A recent analysis has shown that eosinophilic gastritis and eosinophilic duodenitis are severely undiagnosed or misdiagnosed as another GI condition. Allakos Inc. has recently reported the results of this study, which indicated that 45% of their symptomatic patient sample had one of the two conditions.
About the Conditions
These diseases are severe, chronic, inflammatory conditions characterized by an array of symptoms including cramping, bloating, stomach pain, diarrhea, nausea, loss of appetite, weight loss, and vomiting. These symptoms in combination with elevated eosinophils in either the stomach or the patient’s duodenum (the beginning of the small intestine) indicate the disease.
It has also been uncovered that activated mast cells can contribute to the pathogenesis of these illnesses.
Unfortunately, there has yet to be a treatment approved for either of these conditions. While patients can be provided steroids to ease their symptoms, these cannot be used long-term due to various side effects associated with steroid use.
The Study
This study examined levels of eosinophil and mast cells in patients who had either undiagnosed symptoms or one of the following functional gastrointestinal disorders (FGID): irritable bowel syndrome (IBS) or functional dyspepsia (FD). To be included in this study, patients had to either have a minimum of 6 months of ongoing symptoms that were unresponsive to dietary changes or pharmacologic therapies or an IBS or FD diagnosis.
This was the first investigation of its kind, aimed to improve levels of diagnosis among patients.
All of the patients who had a symptom severity score of at least 3 on average each week and a score of at least 10 for the PRO questionnaire underwent an endoscopy with gastric and duodenal biopsies.
Primary endpoints of this trial were the proportion of participants who met the criteria for EG/EoD or who met the criteria for mast cells. Both of these criteria were a minimum of 30 of the respective indicator.
Results
Of the 556 patients initially screened, 405 (73%) fit the severity criteria. Of those biopsied, 181 (45%) met the criteria for EG/EoD. That equates to 33% of the total sample (those biopsied and those not).
50% of the individuals biopsied (204/405) had greater than 30 mast cells/HPF.
Looking Forward
Allakos is currently in the process of developing AK002 (lirentelimab) as a therapeutic option for eosinophil related conditions and mast-cell related conditions.
This therapy targets a receptor called Siglec-8 which is expressed on both eosinophils and mast cells. The investigative therapy has already been granted Orphan Drug Designation from the FDA.
So far, positive results from a Phase 2 trial called ENIGMA have shown promise. The therapy was able to reduce eosinophil counts as well as the severe symptoms that patients were experiencing.
A Phase 3 and a Phase 2/3 study are still ongoing. Researchers expect to release results from these investigations by the second half of next year, and they are hopeful about the possibility of improving the quality of life of patients with these conditions.
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