Celiac disease vaccine Nexvax2 well-tolerated

SAN DIEGO — Nexvax2, a therapeutic vaccine that can protect against gluten exposure in certain patients with celiac disease, was well-tolerated by patients in two phase 1 studies of the vaccine, according to data presented at Digestive Disease Week 2016.

“In the field of autoimmune diseases, antigen-specific immunotherapy is considered the holy grail,” Robert P. Anderson, BMedSc, MB, ChB, PhD, FRACP, chief scientific officer of ImmusanT, and colleagues wrote. “Celiac disease is the first [autoimmune disease]-like disease for which the hierarchy of peptides (epitopes) recognized by pathogenic CD4+ T cells is well-defined.”

The researchers believe that celiac disease is caused by eating gluten primarily for individuals who carry the HLA-DQ2.5 gene. They also believe that individuals with celiac disease possess CD4+ T cells that are gluten reactive. So to treat celiac disease and make a gluten-free diet unnecessary, they have developed Nexvax2, an injectable formulation of three peptides with epitopes that are recognized by the gluten-reactive CD4+ T cells. The researchers believe that injecting these epitopes can cause the CD4+ T cells to become unreactive to gluten.

To evaluate Nexvax2, the researchers randomly assigned 59 patients with celiac disease and the HLA-DQ2.5 gene to 16 doses of either Nexvax2 or placebo, twice a week for 53 days. Before and after treatment, patients underwent a 3-day “gluten challenge.” During this time, the T-cell response of each patient was evaluated.

After 8 weeks, both the Nexvax2 and placebo patients showed similar levels of plasma cytokines and gastrointestinal symptoms. During the second “gluten challenge,” patients failed to reproduce the elevated T-cell response observed during the first challenge. In addition, patients who received Nexvax2 were more likely to complete the “gluten challenge.”

This is the first time an antigen-specific immunotherapy that used peptides has been demonstrated to induce systematic unresponsiveness to the dominant T-cell epitopes in patients with an autoimmune disease-like disease, the researchers wrote.

“These data begin to elucidate the proposed mechanism of action for Nexvax2 in HLA-DQ2.5 [positive] patients with celiac disease,” Leslie Williams, president and CEO of ImmusanT, said in the release. “We look forward to the initiation of a phase 2 study of Nexvax2 using a personalized approach to development in patients with celiac disease.” – by Will Offit

Reference:

Goel G, et al. Abstract #846. Presented at: Digestive Disease Week; May 21-24, 2016; San Diego.

Disclosure: Anderson and Williams are employed by ImmusanT. One researcher reports receiving fees from ImmusanT and Nexpep Pty Ltd. Please see the DDW disclosure list for all other researchers’ relevant financial disclosures.