Provention Bio Begins Phase 2 Study of Non-responsive Celiac Disease Treatment

Provention Bio announced the initiation of the Phase 2b PROACTIVE (PROvention Amgen Celiac ProtecTIVE) study of PRV-015, an anti-interleukin-15 monoclonal antibody, in adult celiac patients not responding to a gluten-free diet, a condition known as 'Non-Responsive Celiac Disease' (NRCD). Provention is developing PRV-015 under its 2018 collaboration with Amgen.

"Celiac disease remains the most prevalent autoimmune disease with no therapeutic treatment, and gluten-free diets are unable to effectively manage the disease in a large subset of patients, given the widespread use of gluten in foods, medications and consumer products, as well as the contamination of apparently 'gluten-free' products," said Peter H.R. Green, MD, Phyllis & Ivan Seidenberg Professor of Medicine; Director, Celiac Disease Center at Columbia University. "The long-term effects of the activation of the immune system by gluten in non-responsive celiac disease can be devastating, including the potential development of intestinal lymphoma. Based on prior data, PRV-015 represents an exciting therapeutic candidate to potentially intercept the damaging effects of contaminating gluten."

"PRV-015 has the potential to be the first-ever approved therapeutic for celiac disease," said Francisco Leon, MD, PhD, Chief Scientific Officer and Co-Founder, Provention Bio. "We believe that PRV-015 is the only investigational candidate that has been shown in clinical studies to simultaneously reduce gluten-induced symptoms and markers of intestinal inflammation as compared to placebo. We look forward to expanding our clinical experience with this candidate, consistent with our mission to bring forward therapies designed to intercept or prevent immune-mediated diseases."

The placebo-controlled, double-blind, randomized study initiated will examine the efficacy and safety of three dose levels of PRV-015 versus placebo, administered every two weeks for six months. The study does not require a gluten challenge and patients are asked to maintain their usual diet. The trial is expected to enroll approximately 220 adults with NRCD across approximately 40 sites in the United States, Canada and Europe. The primary endpoint of the study is the efficacy of PRV-015 as measured by the CeD-PRO (Celiac Disease Patient-Reported Outcome).

PRV-015 has been studied in six completed clinical trials to date. In a prior randomized double-blind, placebo-controlled Phase 2a study in 63 adults with celiac disease, PRV-015 reduced intestinal inflammation and symptoms associated with celiac disease after a controlled gluten challenge as compared to placebo. Specifically, at 12 weeks, a decrease of 38% (p=0.02) % in the CeD-PRO symptom measure and a decrease of 38% (p=0.03) in intestinal intraepithelial lymphocytes was observed.

In November 2018, Amgen and Provention Bio announced a licensing and co-development agreement for PRV-015 (also known as AMG 714). Under the terms of the agreement, Provention will conduct and fund the Phase 2b trial in non-responsive celiac disease (NRCD). Amgen will be responsible for the manufacturing of PRV-015. Upon completion of the Phase 2b trial, Provention will be eligible to receive a $150 million milestone payment, as well as additional regulatory milestone payments and royalties if Amgen continues the development of this product candidate.

PRV-015 (also known as AMG 714) is a novel, fully human anti-IL-15 monoclonal antibody which Provention is developing for the treatment of gluten-free diet non-responsive celiac disease (NRCD). The pro-inflammatory cytokine interleukin 15 (IL-15) has been identified as a major mediator in the pathophysiology of celiac disease. PRV-015 binds to and inhibits IL-15 and has emerged as a leading investigational candidate for the treatment of non-responsive celiac disease, in which patients continue to have disease activity despite an ongoing gluten-free diet. In a Phase 2a clinical trial with 63 celiac patients, data showed a reduction in inflammation and symptoms as compared to placebo after a controlled gluten challenge. Provention is currently evaluating PRV-015 in the Phase 2b PROACTIVE (PROvention Amgen Celiac ProtecTIVE) Study.

Celiac disease is a systemic autoimmune disease triggered by gluten consumption in genetically susceptible individuals. Approximately 1% of the western population is affected by celiac disease. The pathophysiology of celiac disease is characterized by an abnormal immune response to gluten, the main protein present in some of the most common cereals (wheat, barley, rye). Modern diets are increasingly enriched with gluten and it is also used as an additive in processed foods, cosmetics and oral medications. Gluten is also present in trace amounts in foods labeled as "gluten-free", as a tableting excipient, and in certain consumer products. As a result of the difficulty in maintaining total avoidance of gluten while on a gluten-free diet (GFD), gluten contamination causes 50% or more of all diagnosed celiac patients on a GFD to continue to experience disease activity. Patients who continue to have symptoms despite attempting to maintain a GFD are deemed to have NRCD. Approximately 1.5 million patients in the U.S. have NRCD. Celiac disease causes debilitating symptoms and serious medical complications, including intestinal mucosal damage which could lead to intestinal lymphoma. There are no approved medications for celiac disease.