The results of a Phase 2 trial for the celiac disease drug, latiglutenase, a combination of enzymes that break down gluten to encourage the healing of damage in the lining of the small intestine, have proved to be disappointing.
In the trial, one set of patients received the drug, originally called ALV003, while another set was given a placebo. Both groups remained on a gluten-free diet. Dr. Joseph Murray, the lead author of the research describes what happened: “Basically, everyone improved.”
“Each day, patients were given drugs to take and each night, they had to fill out a questionnaire, which may have made them more conscious of their condition,” said Murray, a gastroenterologist at the Mayo Clinic in Minnesota.
He attributes the failure to a “Hawthorne Effect,” in which the subjects of a study alter their behavior because they are aware they are being observed. “The primary endpoint of our study – to show through biopsies that there is healing – was not met.”
Latiglutenase to Re-Focus on Symptoms
Investors fell away after the results of the study were made public. But now, ImmunogenX, the company that purchased the drug last year, has done a “post hoc” re-analysis of the data, which was presented at the Digestive Disease Week meeting in May. The study had been published in the March 2017 edition of Gastroenterology.
The analysis indicates that while latiglutenase may not heal damage, it may help to relieve the symptoms of a group of celiac patients who follow a gluten-free diet but still experience discomfort and pain. The drug would be an adjunct to the gluten-free diet, not a replacement.
“If the original trial had been about reducing symptoms, it would have been a success,” said Jennifer Sealey-Voyksner, the chief science officer at ImmunogenX.
The next step for ImmunogenX is to hold a smaller, shorter trial with a more refined goal. “We’re reversing the primary endpoint on this next trial because at this point, it’s the best way to get the therapy to market,” says Sealey-Voyksner. “The data is already there, We just have to show it.”
2020 Update: In 2019, the short Phase 2 trial showed promising results for latiglutenase in terms of the reduction of severe symptoms and quality of life improvement. Now a second Phase 2 trial is enrolling, to see if those results can be validated.