First patient gets vaccine in new clinical trial, plus cholesterol drug shows promises in celiac disease monitoring
By Amy Ratner
Medical and Science News Analyst
Today, a vaccine to treat celiac disease was given to the first patient participating in a clinical trial designed to test the effectiveness of the new drug.
The launch of the Phase 2 clinical trial of NexVax2, being called RESET CeD, is one of several signs of progress by companies working on new treatments for celiac disease and its management.
These developments also include:
CypCel, by ImmunogenX, was tested in a recently completed longitudinal study, with results presented at celiac disease symposium in Finland.
ZED 1227, by Dr. Falk Pharma GmbH’s and Zedira’s ZED 1227 moved to phase 2 clinical trial
Larazotide Acetate, by Innovate Biopharmaceuticals, is poised to become the first celiac disease drug to reach Phase 3 clinical trials.
Overall, the pace of research into celiac disease treatments has speeded up, though it is still expected to take at least five years before a drug will be available to patients.
NexVax 2, a vaccine to protect celiac disease patients from inadvertent gluten exposure while on a gluten-free diet, is being developed by ImmusanT, a Massachusetts biotechnology company. The RESET CeD trial is designed to determine how well the vaccine works and whether the benefits outweigh any risks. Ultimately, ImmusanT is looking to develop a vaccine that would eliminate the need for the gluten-free diet. In an earlier Phase 1 study, patients were given gradually escalating doses of the vaccine or a placebo, followed by maintenance doses. Results were used to create the dosing regimen being used in RESET CeD trial, which is aiming to enroll approximately 150 patients in the United States, Australia and New Zealand.
“Through this study we anticipate making new insights that will further our ability to demonstrate specific suppression of the immune response to gluten epitopes and associated effects of celiac disease,” said Ken Truitt, M.D., ImmusanT chief medical officer.
In its recently completed study, researchers from the Mayo Clinic tested how well CypCel, a diagnostic test based on simvastatin, a widely-used cholesterol-lowering agent, works in measuring intestinal damage in celiac disease patients.
Simvastatin has the unusual property of being highly metabolized in the small intestine by an enzyme that is expressed on the villi lining the intestine. Participants in the study were given a tablet containing the medication and later provided two blood samples. The concentration of the simvastatin in the samples was found to be directly related to how healthy the villi were. If the villi was healthy, a high metabolism rate led to a reduced concentration of simvastatin in the blood. In patients with damaged villi, the reverse was found.
Simvastatin levels measured at periodic intervals can monitor progressive changes that are indicative of whether a treatment, such as the gluten-free diet, is effective, according to the company.
“We are very excited to be developing this new diagnostic method, which serves as an alternative to an expensive and invasive biopsy,” said Jennifer Sealey Voyksner, ImmunogenX chief scientific officer. ImmunogenX is California company focused on the treatment of celiac disease.
Currently, in the United States, the gold standard for celiac disease diagnosis calls for blood tests, followed by a biopsy to determine if there is damage to the absorbing villi.
ZED 1227 would work by blocking an enzyme that reacts with fragments of gluten and makes them more recognizable to the cells that cause destruction of the nutrient-absorbing villi in those who have celiac disease.
The enzyme, tissue transglutaminase (tTG), makes the harmful gluten protein that passes through the intestinal lining more palatable and more recognizable to T-cells. TTG has a direct role in the gut lining where it enhances the inflammatory activity of gluten. By blocking tTG, ZED 1227 would prevent the immune response that drives celiac disease.
Research into ZED 1227 recently advanced to a Phase 2 clinical study, which will test how well the pill works and at what dose. It is being developed by Dr. Falk Pharma, a company that specializes in the development of drugs used in gastroenterology. Zedira, a clinical-stage bio-tech company with a focus on celiac disease and transglutaminase, is also involved.
Innovate, a clinical stage biotechnology company focused on developing novel medicines for autoimmune and inflammatory diseases with unmet needs, is expected to begin Phase 3 clinical trials by the end of the year for use of larazotide acetate to treat celiac disease. In previous phases of clinical study in more than 600 patients, larazotide acetate was found to be safe compared to a placebo, according to the company. The drug is designed to work by decreasing intestinal permeability and regulating tight junctions between intestinal cells. This so-called “leaky gut” is thought to be the gateway to many autoimmune diseases, including celiac disease.
Larazotide acetate could potentially help those who have symptoms even though they follow a gluten-free diet, currently the only treatment for celiac disease. When taken before a meal, larazotide acetate may help keep the tight junctions closed, reducing the inflammatory intestinal response triggered by the gluten protein in wheat, barley and rye in those who have celiac disease.