PRV-015 (formerly AMG 714) is a novel anti-IL-15 monoclonal antibody which Provention is developing for the treatment of gluten-free diet non-responsive celiac disease (NRCD). Provention plans to advance PRV-015 into a Phase 2b clinical trial in NRCD.
PRV-015 (AMG 714) was initially developed by Amgen in rheumatoid arthritis. In 2015, Amgen outlicensed AMG 714 to Celimmune LLC, a clinical development-stage immunotherapy company founded by Provention’s CEO, Ashleigh Palmer, and Chief Scientific Officer, Francisco Leon, MD, PhD. Celimmune conducted two separate AMG 714 Phase 2a clinical trials in NRCD and refractory celiac disease type II, after which Amgen acquired Celimmune in 2017. Data from both clinical trials were presented at Digestive Disease Week® (DDW) 2018.
Celiac Disease Interception
Celiac disease is a chronic hereditary systemic autoimmune and inflammatory disease triggered by gluten consumption that results in damage to the lining of the small intestine, causing gastrointestinal dysfunction and debilitating symptoms. Nutritional malabsorption can lead to a failure to thrive in children and anemia and osteopenia in adults. Over the course of a lifetime, untreated or poorly managed celiac disease is often associated with deteriorating general health, multiple serious intestinal and extra-intestinal medical complications, and increased morbidity and mortality. It is estimated that currently 1% of Western and 0.5% of Asian populations suffer from celiac disease and diagnosed prevalence is expected to increase with improved diagnostic tools and clinical awareness. There are no approved medications for celiac disease.
Provention believes that AMG 714, an anti-IL-15 monoclonal antibody, offers the potential to “intercept” the progression of celiac disease.
Abadie, V., et al. IL-15, gluten and HLA-DQ8 drive tissue destruction in coeliac disease. Nature (2020).
Cellier C et al. Safety and efficacy of AMG 714 in patients with type 2 refractory coeliac disease: a phase 2a, randomised, double-blind, placebo-controlled, parallel-group study. Lancet Gastroenterol Hepatol. 2019 Dec;4(12):960-970. doi: 10.1016/S2468-1253(19)30265-1. Epub 2019 Sep 4.
Lähdeaho ML et al. Safety and efficacy of AMG 714 in adults with coeliac disease exposed to gluten challenge: a phase 2a, randomised, double-blind, placebo-controlled study. Lancet Gastroenterol Hepatol. 2019 Dec;4(12):948-959. doi: 10.1016/S2468-1253(19)30264-X. Epub 2019 Sep 4.
Syage JA, et al., Determination of gluten consumption in celiac disease patients on a gluten-free diet. Am J Clin Nutr. 2018 Feb 1;107(2):201-207.
Guandalini S, et al., Direct Costs in Patients with Celiac Disease in the USA: A Retrospective Claims Analysis. Dig Dis Sci. 2016 Oct;61(10):2823-2830.
Ettersperger J, et al., Interleukin-15-Dependent T-Cell-like Innate Intraepithelial Lymphocytes Develop in the Intestine and Transform into Lymphomas in Celiac Disease. Immunity. 2016 Sep 20;45(3):610-625.
Shah S et al., Patient perception of treatment burden is high in celiac disease compared with other common conditions. Am J Gastroenterol. 2014 Sep;109(9):1304-11.
Abadie V, Jabri B. IL-15: a central regulator of celiac disease immunopathology. Immunol Rev. 2014 Jul;260(1):221-34.
Malamut G, et al., IL-15 triggers an antiapoptotic pathway in human intraepithelial lymphocytes that is a potential new target in celiac disease-associated inflammation and lymphomagenesis. Clin Invest. 2010 Jun;120(6):2131-43.