Celiac disease (CD) is an autoimmune disorder of the small intestine resulting from intolerance to gluten proteins and it afflicts nearly 1% of most populations (Schuppan 2009, Rubio Tapia 2010). The principal physiology is villous atrophy in the small intestinal epithelium triggered by the ingestion of cereal grains, such as wheat, rye, or barley. CD has no known cure and the only effective therapy is adherence to a lifelong gluten-free diet (GFD). Yet in practice it is virtually impossible to totally avoid gluten (Syage 2018). Patients are continuously exposed to low levels of gluten that can cause symptomatic pain and suffering and persistent histologic damage that can lead to other long-term health issues such as lymphoma, bowel cancer, osteoporosis, anemia, malnutrition, etc. (Kelly 2015, Green 2015). The burden of the disease is enormous on the individuals as well as their family and friends, who must adjust to the dietary and recovery needs of CD individuals. Thus, there is an acute need for non-dietary therapies for celiac disease.
The 3rd Gastroenterology Regulatory Endpoints and Advancement of Therapeutics (GREAT-3) conference sponsored by the FDA in 2015 specifically cited the need to develop treatments that address symptom distress due to inadvertent gluten ingestion and made a clear case for the need of measurement outcome tools relevant to the suffering of CD patients (Leffler 2015).
Latiglutenase is an Active and Safe Drug
ImmunogenX is developing Latiglutenase (IMGX003), a mixture of two gluten-specific recombinant proteases that degrades gluten proteins into small physiologically irrelevant fragments, and is to be administered as an adjunct to a gluten-free diet (GFD). In Phase 2a and 2b trials Latiglutenase has been shown to mitigate gluten-induced intestinal mucosal injury as well as effect symptomatic improvements in clinical trials. The efficacy for symptom relief was particularly pronounced for patients who remain seropositive despite a GFD as seen in the results below (Syage 2017). These studies also showed that Latiglutenase is well tolerated by CD patients with no discernable difference in adverse events for treated patients vs. placebo patients.
Schuppan D, Junker Y, Barisani D. Celiac disease: from pathogenesis to novel therapies. Gastroenterology 2009;137:1912–33.
Rubio-Tapia A, Murray JA. Celiac disease. Curr Opin Gastroenterol 2010;26:116–22.
Kelly CP, Bai, JC, Liu E, Leffler DA. Celiac disease: clinical spectrum and management. Gastroenterol 2015;148:1175-1186.
Green PHR, Lebwohl B, Greywoode R. Celiac disease. J Allergy Clin Immunol 2015;135:1099-1106.
Syage JA, et al. Determination of gluten consumption in celiac disease patients on a gluten-free diet. Am J Clin Nutr 2018;107:201-207.
Leffler D, Kupfer SS, Lebwohl B, Bugin K, Griebel D, et al., Development of Celiac Disease Therapeutics: Report of the Third Gastroenterology Regulatory Endpoints and Advancement of Therapeutics Workshop. Gastroenterology 2016;151:407 – 411.
Syage JA, Murray JA, Green PHR, Khosla, C. Latiglutenase Improves Symptoms in Seropositive Celiac Disease Patients While on a Gluten-Free Diet. Dig Dis & Sci 2017;62:2428-2432.