Pharma

Celiac disease immunotherapy that would replace a gluten-free diet begins clinical trials

A new, potential disease-altering drug treatment for celiac disease would eliminate the need for a gluten-free diet in certain patients with celiac disease.

Cambridge, Massachusetts drug company ImmusanT‘s drug, which has begun clinical trials in the U.S., aims to interfere with the immune response to gluten. Nexvax2 uses a series of peptides to reprogram T-cells triggered by gluten, a protein found in wheat, barley and rye, in those with celiac disease.

In these patients, the body’s immune response to gluten affects the process of the small intestine and can inhibit the absorption of nutrients into the body and can potentially cause a host of deficiency complications. No medicines are available for the autoimmune disorder, and it’s typically managed with a gluten-free diet.

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ImmusanT has initiated a randomized, double-blind, placebo-controlled phase 1 study in the U.S. to establish the safety, tolerability and pharmacokinetic profile of its drug as well as a second phase 1 trial in Australia and New Zealand (a phase 1 safety trial has already been conducted overseas). The U.S. trials will target patients with diagnosed celiac disease (confirmed by a gastric biopsy) who carry the gene HLA-DQ2, which has been linked to the presence of celiac disease. Only patients with that gene – about 80 percent to 90 percent of the celiac population – would be helped by Nexvax2, according to ImmusanT CEO Leslie Williams.

Along with the drug, ImmusanT has developed a companion blood test to identify HLA-DQ2 celiac patients. “It’s a fairly common genetic subtype, and it doesn’t mean that a patient definitely has celiac, but it’s a rule-out test,” Williams said. “If they don’t have the gene, they don’t have celiac disease. That is one of the key things that we want to bring to attention.”

Williams said the U.S. trial will be completed within 12 to 18 months, and the company will then continue with the necessary trials to secure U.S. and overseas regulatory approval.

To get this far, ImmusanT raised a $1 million seed round followed by a  $20 million series A from Vatera Healthcare Partners in 2011 to carry it through initial clinical trials.

Formed in late 2010, the company’s co-founders are Williams and the technology’s inventor, Dr. Bob Anderson, a gastroenterologist who had been working on it for more than a decade in Europe and Australia, and had formed the company Nexpep Pty. Ltd. in Melbourne before connecting with Williams. “I became very interested in the technology because of the market itself — it’s a huge market and it goes undiagnosed a considerable amount of the time, so there’s huge opportunity to help patients,” Williams said. “And the technology was game changing because of the approach to modifying the disease itself.”

About 1 percent of the U.S. population is expected to have celiac, but many of them go undiagnosed, and many other people eat a gluten-free diet without a celiac diagnosis. This disconnect between diagnosis and treatment is part of the reason why ImmusanT’s diagnostic companion is such an important part of the technology, Williams said, and such a differentiator from other companies developing celiac drugs.

Alba Therapeutics is enrolling for a phase 2b clinical study of its lead candidate, larazotide acetate, which is designed to reduce the inflammatory process in response to gluten, although the company suffered some early setbacks. Another phase 2 company, Alvine Pharmaceuticals, takes an approach that involves a digestive enzyme that can help break down gluten before the immune system reacts to it. The drug received fast-track designation from the U.S. Food and Drug Administration, but is intended to be used alongside a gluten-free diet.

“Fortunately, with the advent of different technologies in clinical development, you’ve got an enzyme, you’ve got a drug that is targeting the leaky gut, and now you’ve got our vaccine, and there’s other diagnostic technology being developed,” Williams said. “The field is advancing very rapidly with the knowledge and understanding of the disease itself.”

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