Celiac Disease Cure? ImmusanT Tests Nexvax2 in Clinical Trials

Update (July 2, 2019): Last week, ImmusanT halted the Phase II trial evaluating the efficacy of Nexvax2. According to a press release, an interim analysis revealed the drug candidate was no better at protecting celiac disease patients from gluten exposure compared to placebo.

Originally published on June 10, 2019:

Have you ever tried eating a gluten-free diet? Some may have tried it for fun, but for others, it’s the only option they’ve got. Today, about 2-3 million people in the US must stick to a gluten-free diet because of celiac disease.

Celiac disease is an autoimmune reaction triggered by gluten proteins found in foods like wheat, rye and barley. The reaction leads to chronic inflammation in the intestine in addition to acute symptoms like nausea, abdominal pain and headaches.

There is no pharmacologic cure for celiac disease, just a strict gluten-free diet. But it’s not easy living this way.

“Given the pervasiveness of grains in the US diet, it’s nearly impossible to maintain a strict gluten-free state,” said Dr. Ken Truitt, Chief Medical Officer of ImmusanT, Inc. “This creates a lot of complications for patients beyond the medical ones. Patients can find the gluten-free diet socially isolating…they have to worry about ingesting gluten every time they dine outside their home.”

Because patients will inevitably ingest gluten, even the smallest amount — just a pinch — can contribute to ongoing inflammation and intestinal damage. Moreover, they are also more susceptible to osteoporosis and gastrointestinal cancer as a consequence of chronic inflammation in the intestine. Clearly, there is an unmet need to provide more adequate control for people with celiac disease.

ImmusanT scientists are hoping to provide a better solution for people with this disease. They are testing a treatment known as Nexvax2 that selectively modifies the immune response to gluten and improves tolerability to gluten.

The drug works the same way a parent might get their child (who hates vegetables) to eat vegetables. If a mother fills her son’s diet with lots of broccoli each meal, he may grow to tolerate it (and maybe even enjoy it).

Similarly, Nexvax2 works by exposing the immune system to three specific peptides, or short protein fragments, found in gluten that are primarily responsible for triggering the immune response in patients with celiac disease.

“If you bathe specific T cells in the offending antigen, paradoxically it can cause T cells that ordinarily promote a specific pro-inflammatory response to shut down,” explained Truitt. “In animal models, you can generate suppressive populations of T cells [which] have the specific function of downregulating the immune response.”

The inflammatory biomarker data from the group’s early clinical work is consistent with this theory. The hope is that a decreased inflammatory response will result in clinical benefit.

Now, they are working on a Phase II trial that addresses the problem of periodic exposure to gluten in patients following a gluten-free diet.

“We are testing to see whether we can treat patients with Nexvax2 and then expose them to gluten and see a reduction in symptoms and biomarkers that would indicate an underlying inflammatory response,” said Truitt.

The drug is administered twice a week subcutaneously, dampening the inflammatory response over time. As the gut epithelium turns over, healthy tissue will replace the damaged tissue and eventually, the gut might revert to completely normal histology. In the future, Truitt says they may test if Nexvax2 treatment can help patients relax their gluten-free diet or in some cases, revert to a normal diet. While the Phase II studies are now underway, the company could file for regulatory submission in a few years.

“Nobody has successfully created a drug that has an indication for treating celiac disease,” he added. “Because we are first, we have to blaze that path with the FDA and other regulators.”

Sitari Pharmaceuticals, Celimmune and ImmunogenX offer their own candidate drugs for treating celiac disease. Recently, ImmunogenX, a subsidiary of Immunogenics LLC, began a Phase II trial for Latiglutenase, a modified enzyme that digests gluten.

Given the limited treatment options, people with celiac disease are eager for a new solution.

“I’ve been in the drug development business now for over a couple of decades, and I have never worked with a group of patients that is so interested, dedicated and selfless in their desire to help find a treatment,” said Truitt. “I think this reflects a very high degree of frustration on the patient’s part, as well as the magnitude of unmet need.”