Every year, our editorial staff head to Digestive Disease Week. It is the largest international gathering of physicians, researchers and academics in the fields of gastroenterology, hepatology, endoscopy and gastrointestinal surgery. It’s where we get the latest and greatest research for celiac disease and non-celiac gluten sensitivity. It’s where the movers and shakers in celiac research launch their abstracts and talk about new research in the field of celiac disease. This year, we’re headed to Washington DC to learn about this research, and also to eat at some of the many gluten-free restaurants in DC! Thank you, DDW, for providing a platform for the experts to present this outstanding research.
We had the pleasure of attending a pre-Digestive Disease Week conference call where they previewed some of the research that we’ll be hearing about during the conference. A very special research project that we’ve been following for years is getting some major traction – and we’re excited to tell you about it.
With any research that is in early phase clinical trials, it’s important to note that this project is not finalized yet. This means that this product may or may not come to the market, depending on how clinical trials go. While we’re all excited about the advances in celiac research, what we have right now it’s just that – research. We’re all excited for a potential cure or pharmaceutical intervention, but it’s still a waiting game.
“A gluten-free diet has been the only treatment option for celiac disease patients to date, yet it is nearly impossible for them to avoid gluten entirely and indefinitely,” said Markku Maki, MD, PhD, the principal investigator and a professor for the Faculty of Medicine and Biosciences at the University of Tampere in Finland. “An average of half of all celiac disease patients on a gluten-free diet continue to have mucosal inflammation or damage, and a third have recurrent symptoms. That is why we have been investigating medications to help prevent the consequences of hidden gluten.”
Francisco Leon MD presented about AMG 714 (also known as ANTI-IL-15 MAB). This project offers hope for celiac patients who are inadvertently exposed to gluten (i.e., NOT cheating and eating gluten outright). This ameliorates the effects of gluten consumption in celiac disease. He reported that they just finished a phase 2a, randomized, double-blind, placebo-controlled study evaluating AMG 714 in adult patients with celiac disease exposed to a high-dose gluten challenge. This drug reduced activation of the immune system, leading to fewer symptoms due to intestinal damage. It’s a subcutaneous injection of a biologic immune modulator that blocks Interlukin 15 (IL-15) that is a mediator of celiac disease.
“It’s important to note that this drug is being investigated for its potential to protect against modest contamination, not deliberately eating large amounts of gluten, like bread or pasta,” said Francisco Leon, MD, PhD, the study director and consultant for Amgen. “Contamination, which can happen during food processing or packaging, during cooking, or due to inadequate labelling, is known to occur very frequently, despite following a gluten-free diet. Our hope is that this drug may allow celiac patients on a gluten-free diet to experience fewer gluten-triggered events.”
Want to know the details of the study design? Read on!
“This randomized, double-blind, placebo-controlled, phase 2a study compared the effects of AMG 714 at two dose levels (150 mg and 300 mg) to a placebo among celiac disease patients over a 12-week period. The drug was administered six times by subcutaneous injection. A subset of patients received a high-dose gluten challenge of approximately 2.5 grams per day for 10 weeks. Another sub-group of patients, who showed mucosal atrophy at baseline, were found — with novel stool and urine gluten detection tests — to be exposed to hidden gluten contamination during their regular gluten-free diets and did not receive the additional gluten challenge.
The results show that AMG 714 reduced gluten-triggered effects in each of the two groups receiving the drug, compared to placebo. While AMG 714 did not fully prevent gluten-induced mucosal injury in the gluten challenge group, the primary endpoint of the study, a decrease in intestinal inflammation was observed, as well as a non-significant trend towards reduced intestinal damage in the non-challenge group. Reduction in symptoms was observed when patient-reported outcomes were assessed, especially for the group that took the larger 300 mg dose. While the placebo group experienced an increase in diarrhea, it was not seen in patients who took the drug. At week 12, none of the patients given the gluten challenge who took the 300 mg dose was deemed by the principal investigator to have active disease, compared to one third of the placebo group. In the group that did not receive the gluten challenge, no symptoms associated with accidental gluten consumption were observed. Importantly, there were no serious adverse events or safety signals in the study. The most frequently reported adverse events related to the study drug included injection site reactions and pain, headache and upper respiratory tract infection. No dose-related trends were evident except for injection site reactions.”
We can’t wait to hear more about this study during Digestive Disease Week, as Dr. Leon will be presenting on June 4th at DDW.
Disclosure: The study was funded by Celimmune, a biopharmaceutical company acquired by Amgen after completion of the study.Originally posted May 2018