Patients with celiac disease treated with larazotide acetate experienced improvements in GI symptoms and non-GI symptoms such as headache and fatigue, as well as significant reductions in the number of symptomatic days.
Larazotide acetate 0.5 mg has the potential to be the first pharmacologic treatment for celiac disease, a genetic autoimmune condition affecting 1% of the western population.
Treatment with larazotide acetate 0.5 mg three times a day reduced GI and non-GI symptoms in a study of more than 800 patients while also reducing the number of symptomatic days (the days on which patients reported significant symptoms) by 26% through the duration of the study, an effect not seen at higher doses.
Conversely, treatment with larazotide acetate 0.5 mg increased by 31% the number of days patients reported few to no symptoms.
The safety and tolerability profile of Larazotide acetate was comparable to placebo. No treatment-related serious adverse events were reported.
This study represents the first large therapeutic trial in celiac disease to meet its primary endpoint of reducing signs and symptoms of celiac disease and is the first successful trial of a novel class of agents targeting Tight Junctions regulation, according to Joseph Murray, MD, with Mayo Clinic.
In the study, the large majority of participants were women (mean age 45 years) who had been on a gluten-free diet for an average of 5 years, so they were patients experienced with managing their disease and treatment.
Larazotide acetate also significantly reduced non-GI symptoms such as headache and tiredness commonly reported by celiac patients.
Because it is triggered by ingesting gluten, celiac disease is usually managed by a lifetime gluten-free diet. But up to 72% of people with celiac disease have recurrent symptoms from inadvertent exposure to gluten in foods or everyday products (such as medicines, vitamins, lip balm, etc) or straying from their gluten-free diet.
In addition to affecting quality of life, the disease comes with increased risk of GI cancers and T-cell lymphoma.
“Celiac disease represents a significant unmet medical need,” Murray said. “It is increasing in prevalence worldwide and there is no standardized measure of response to therapy to conduct clinical trials.”
The primary endpoint of the study was reduction of GI symptoms using the celiac disease-specific domains of the GSRS (Gastrointestinal Symptom Rating Scale) includingdiarrhea, indigestion, and abdominal pain at the dose of 0.5 mg. This response was sustained through the active phase of the study, Murray said.
Treatment with larazotide acetate 1 mg and 2 mg was not effective, Murray said. “That’s consistent with all of the clinical challenge studies done previously. It was always the lowest dose used that was the most effective,” he said.
In light of these positive trial results, Murray said larazotide acetate 0.5 mg warrants further investigation in phase III clinical trials.