It’s no longer a pipe dream to wish for an alternative to the gluten-free diet. Close to a dozen potential celiac disease treatments are in the works—and a few are on the cusp of reaching major milestones on the pathway to drug development.
If you’ve been waiting for the day you can sink your teeth into a warm glazed doughnut—or at least not worry about cross-contamination in restaurants—that day isn’t tomorrow. But it’s coming, say celiac experts.
To bring a new drug to market, the FDA requires a successful sequence of clinical trials—denoted by Phases 1 through 3—to prove that the drug is both safe and effective. On average, this process takes 12 years.
“It’s a frustratingly slow process for any drug and this is compounded for a disease like celiac disease that’s never had a drug treatment before,” says Daniel A. Leffler, MD, MS, director of research at The Celiac Center at Beth Israel Deaconess Medical Center in Boston. “When developing a drug for celiac disease, everything has to be figured out from scratch. For example, we haven’t had an accepted survey tool for measuring gastrointestinal symptoms that’s validated for celiac disease clinical trials, so that has had to be developed—and that alone takes years.”
Despite these hurdles, the field of potential celiac pills is surprisingly large. That’s in part because we know quite a lot about the biology of celiac disease, says gastroenterologist Joseph Murray, MD, a celiac expert at the Mayo Clinic in Rochester, Minnesota. “We know what steps occur and lead to damage, so we have lots of possible targets.”
One celiac pill works by tightening loose junctions in the gut, so gluten can’t slip past. Another chops up gluten, so the immune system doesn’t recognize it. Some bind to gluten, so it never gets digested and we can, well, “poop it out.” The buzzed-about “egg yolk pill” binds to gluten and mops it up with antibodies produced in egg yolk. (It turns out chickens can produce antibodies to just about anything, including gluten, and these get expressed in the egg yolk.)
But two drug candidates—ALV003 from Alvine Therapeutics and AT-1001 from Alba Therapeutics—lead the pack. These drugs have been in the development pipeline the longest and have been tested on hundreds of patients in Phase I and Phase 2 studies across the United States and Europe. According to Leffler, either one of these drugs could potentially enter Phase 3 trials very soon. This would be a very big first for a celiac drug. Phase 3 trials are not only the largest clinical trials, they’re the last step before seeking approval from the FDA. It takes an average of three years from the start of a Phase 3 study to FDA approval, assuming the drug works as intended.
Both ALV003 and AT-1001 are designed to handle gluten cross-contamination; they do not take the place of the gluten-free diet.
“There’s no shortage of occasions—traveling, work events, dinner at the in-laws—when despite best precautions, it’s difficult to avoid gluten completely,” says Leffler.
Either drug, formulated as capsules, could be taken as needed in these scenarios. They could also be used on a more regular basis for those celiac individuals who don’t fully respond to the gluten-free diet.
“We see lots of patients with persistent symptoms, nutritional deficiencies and ongoing intestinal inflammation despite good efforts with the gluten-free diet,” says Leffler. “For them, a drug treatment could augment the gluten-free diet to help it work better and faster.”
The Celiac Drug Holy Grail
There is hope for the holy grail of celiac drug development: Two drugs—COUR-NP-GLI and NexVax2—aim to replace the gluten-free diet entirely.
In COUR-NP-GLI, toxic gluten peptides are repackaged into tiny particles called “nanoparticles,” which, once processed in the body, reprogram the immune system’s T-cells to ignore gluten. In animal models of celiac disease, COUR-NP-GLI was given intravenously and results were promising. Treated animals did the same or better than animals maintained on a gluten-free diet. However, COUR-NP-GLI has yet to be tested in humans. Its manufacturers, who presented their findings at the 2015 International Celiac Disease Symposium in Prague, hope to begin human trials in the near future.
NexVax2, which has been likened to “allergy shots” for celiac disease, also aims to turn off the immune response to gluten. It accomplishes this via a series of shots of small gluten peptides (proteins) delivered through the skin. Testing of NexVax2 in human trials started several years ago in Australia. A new clinical trial, again in Australia, began in late 2015. It’s still in the Phase I stage, which focuses more on drug safety than efficacy. (See chart at right for more details.)
“We’re a long way from proving NexVax2 works, but at least it seems relatively safe,” says Murray. “If it works, it could be a home run and make patients with celiac disease tolerant to gluten. It would be a passport to eating gluten with impunity.”