Results of a randomized, double-blind, placebo-controlled clinical trial to assess the markers of potential efficacy and safety of the investigational medicine in 34 adults with proven celiac disease was presented today as a late-breaking abstract at UEG Week 2019, Barcelona, Spain. At inclusion, patients had well-controlled biopsy proven celiac disease. After inclusion, they underwent an oral gluten challenge. Based on the study, Takeda exercised its option to acquire the exclusive global license to TAK-101.
“While many people living with celiac disease can manage their symptoms by following a gluten free diet, there are currently no treatment options for those who continue to have symptoms,” said Asit Parikh M.D., Ph.D., Head, Gastroenterology Therapeutic Area Unit at Takeda. “Our collaboration with COUR has shown, for the first time, that it is possible to induce specific immune tolerance to a foreign antigen in autoimmune diseases such as celiac disease. With our expertise in inflammatory diseases, Takeda is well positioned to further develop TAK-101 in pursuit of providing the first approved treatment option for patients with celiac disease.”
In the trial, treatments were administered intravenously on day 1 and day 8. The gluten challenge began seven days after the second treatment administration and included 12 grams of gluten per day for three days followed by 6 grams of gluten per day for 11 days. The primary endpoint was change from baseline in interferon-gamma (IFN-γ) spot forming units (SFUs) at day 6 after gluten challenge using a gliadin-specific enzyme-linked immunospot (ELISpot) assay. This test is a direct measure of gluten-specific systemic T cell activation in celiac disease, and blocking this response suggests individuals with celiac disease could be protected from the effects of gluten exposure. 34 patients were randomized and treated, 6 discontinued due to gluten related symptoms, and 28 completed the 14-day gluten challenge per protocol.
The primary endpoint of the trial was achieved with a mean change from baseline in IFN-γ ELISpotSFUs of 2.10 and 17.57 with TAK-101 and placebo, respectively (p=0.0056). Also seen was a trend in protection from small intestinal mucosal damage with deterioration of 0.18 with TAK-101 compared with 0.63 with placebo (p=0.079). The most frequent adverse events in patients receiving TAK-101 that exceeded the frequency seen in placebo treated patients were nausea, headache, abdominal pain, and back pain. No patient had clinically significant changes in vital signs, routine clinical labs, or serum cytokines/chemokines, gliadin-specific T cell proliferation and cytokine secretion.
Takeda intends to initiate a dose-ranging study to further explore the potential of TAK-101 in the treatment of patients with celiac disease on a gluten free diet to inform future registrational trials. COUR is eligible to receive up to $420 million in future payments, and royalties on sales of any commercialized products resulting from the license.
“We are encouraged by the data from this first human proof of concept study of our proprietary nanoparticle platform designed to reprogram the immune system,” said John J. Puisis, CEO of COUR Pharmaceuticals. “As Takeda assumes responsibility for the celiac disease program, COUR will focus on advancing our pipeline of therapies for a variety of other immune disorders ranging from multiple sclerosis to peanut allergy.”
COUR’s proprietary immune modifying nanoparticles bind inflammatory cells to initiate tolerogenic immune reprogramming. The interior core can be loaded with disease specific antigen – in this case, gliadin proteins – to induce tolerance in autoimmune conditions like celiac disease.
About Celiac Disease
Celiac disease is a genetically driven chronic immune-mediated disorder where abnormal immune responses to gluten peptides lead to small intestinal mucosal damage.1,2,3 Recent population-based studies in the U.S. indicate that the prevalence of celiac disease is around 1%4 and approximately 0.5% globally.5 The threshold of daily gluten that will cause mucosal injury in both adults and children is 10 to 50mg per day – or about 1/100th of a slice of bread.6,7 Celiac disease can cause symptoms including abdominal pain, diarrhea, nausea, and vomiting. Long-term complications of celiac disease may include malnutrition, accelerated osteoporosis, nervous system problems and problems related to reproduction. Currently the only available treatment for patients with celiac disease is maintaining a gluten-free diet, which involves strict, lifelong avoidance of exposure to gluten proteins from wheat, barley, and rye, which is not always effective.8
Takeda’s Commitment to Gastroenterology
Gastrointestinal (GI) diseases can be complex, debilitating, and life-changing. Recognizing this unmet need, Takeda and our collaboration partners have focused on improving the lives of patients through the delivery of innovative medicines and dedicated patient disease support programs for over 25 years. Takeda aspires to advance how patients manage their disease. Additionally, Takeda is leading in areas of gastroenterology associated with high unmet need, such as inflammatory bowel disease, acid-related diseases, and motility disorders. Our GI Research & Development team is also exploring solutions in celiac disease and liver diseases, as well as scientific advancements through microbiome therapies.
About COUR Pharmaceuticals
COUR Pharmaceuticals is developing first-in-class therapies designed to reprogram the immune system to achieve antigen-specific tolerance for immune-mediated disease. COUR’s platform of immune-modifying nanoparticles treats the root cause of immune disease unlike traditional approaches, which only minimize symptoms using toxic immune suppression. COUR’s lead product for celiac disease, partnered with Takeda, is the first demonstration of induction of antigen-specific immune tolerance in any autoimmune disease. Data from clinical and preclinical settings demonstrate the opportunity for the COUR nanoparticle platform to address a wide range of immune and inflammatory conditions. The underlying technology was acquired from Northwestern University and draws from more than 30 years of research by the laboratory of Stephen D. Miller, Ph.D., the Judy E. Guggenheim Research Professor of Microbiology-Immunology. For more information, visit www.courpharma.com.
About Takeda Pharmaceutical Company Limited
Takeda Pharmaceutical Company Limited (TSE:4502/NYSE:TAK) is a global, values-based, R&D-driven biopharmaceutical leader headquartered in Japan, committed to bringing Better Health and a Brighter Future to patients by translating science into highly-innovative medicines. Takeda focuses its R&D efforts on four therapeutic areas: Oncology, Gastroenterology (GI), Rare Diseases and Neuroscience. We also make targeted R&D investments in Plasma-Derived Therapies and Vaccines. We are focusing on developing highly innovative medicines that contribute to making a difference in people's lives by advancing the frontier of new treatment options and leveraging our enhanced collaborative R&D engine and capabilities to create a robust, modality-diverse pipeline. Our employees are committed to improving quality of life for patients and to working with our partners in health care in approximately 80 countries and regions.
For more information, visit https://www.takeda.com
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2 Molberg O, McAdam S, Lundin KE, et al. T cells from celiac disease lesions recognize gliadin epitopes deamidated in situ by endogenous tissue transglutaminase. Eur J Immunol 2001;31:1317-23.
3 Dieterich W, Ehnis T, Bauer M, et al. Identification of tissue transglutaminase as the autoantigen of celiac disease. Nat Med 1997;3:797-801.
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6 Might gluten traces in wheat substitutes pose a risk in patients with celiac disease? A population-based probabilistic approach to risk estimation. Am J Clin Nutr 2013;97:109-16.
7 Catassi C, Fabiani E, Iacono G, et al. A prospective, double-blind, placebo-controlled trial to establish a safe gluten threshold for patients with celiac disease. Am J Clin Nutr 2007;85:160-6.
8 https://www.niddk.nih.gov/health-information/digestive-diseases/celiac-disease/symptoms-causes (accessed October 9, 2019)
