Deborah Ceizler, CDF Chief Development Officer, recently attended the Development of Therapies for Celiac Disease Conference hosted by the Celiac Disease Center at Columbia University. The conference provided a unique opportunity to bring together experts from around the world – physicians, scientists, industry leaders including pharmaceutical, diagnostic, biotechnology and food & agriculture – and patients seeking to learn more about celiac disease and the development of non-dietary therapies for the disease.
Currently, the typical treatment for a patient diagnosed with celiac disease is a strict gluten-free diet for life. Keeping to a diet completely free of gluten can be very costly and challenging. Many patients’ intestines don’t heal completely while on a gluten-free diet, most often due to a failure to adhere to the gluten-free diet strictly enough. Future therapies currently in the pipeline hope to make living with celiac disease less of a burden.
Two of these treatments directly target gluten as it is ingested. The first, from Alvine Pharmaceuticals, is called ALV003. In humans, gluten does not get completely digested, and a specific 33-amino acid-long chain left over is thought to be the main culprit behind celiac patients’ abnormal immune response to gluten. The drug ALV003 is a mixture of two proteins that are able to do what other digestive enzymes cannot: break up that 33-amino acid-long chain. ALV003 has already completed phase 1 and phase 2a studies and is currently undergoing phase 2b trials designed to evaluate how different dosages affect mucosal healing in celiac patients.
The other treatment that directly targets gluten comes from the Israeli company BioLineRx. Their strategy involves a drug they call BL-7010 which is a large, non-absorbable polymer. Instead of helping fully digest gluten, it binds tightly and specifically to the part of gluten that elicits an immune response, gliadin. After binding to the gliadins in the digestive system, the drug then passes through, preventing gliadin from entering the blood. BL-7010 has shown to reduce the immune response in mice models of celiac disease but has yet to complete phase 1 or phase 2 trials in human patients.
Alba Therapeutics is pursuing a different target in its efforts to help those afflicted with celiac disease. A phase 2b trial has recently been completed for larazotide acetate with plans for phase 3 trials now in the works. Larazotide acetate is a molecule that can regulate tight junctions in the body. Using a compound like larazotide acetate to keep tight junctions in the digestive tract from becoming “leaky” helps prevent the immunogenic peptides in gluten from crossing through the intestinal tissue, causing the immune reaction associated with celiac disease.
The final therapy discussed here is currently being investigated by ImmusanT. Called NexVax2, ImmusanT researchers hope that this therapeutic vaccine will help celiac disease patients tolerate gluten. This treatment will only work for the approximate 90% of celiac disease patients with the HLA DQ2 serotype, as opposed to those with HLA DQ8. Nexvax2 has been shown to induce immune tolerance to gluten in mice models of celiac disease and has also completed phase 1 trials.
With these and other therapies currently being researched, patients with celiac disease should have a positive outlook on the future of celiac disease treatment.
Celiac Disease Foundation thanks Dr. Peter Green, CDF Medical Advisory Board member, and his staff at the Celiac Disease Center at Columbia University for hosting this ground-breaking conference.