A vaccine that could enable people with celiac disease to safely consume gluten has begun phase 2 testing in the US, Australia, and New Zealand after more than a decade of development.
Results from several phase 1 trials previously showed that the immune system-modifying treatment, called Nexvax2, is safe and tolerable. The upcoming studies will evaluate its efficacy.
Nexvax2 reprograms T-cells so that they no longer attack certain amino acid sequences – peptides – within the proteins that constitute gluten by repeatedly exposing the body to modified forms of three of these peptides. (Gluten is not one molecule, but rather a composite compound made of several different energy and mineral-rich proteins that, alongside starch, are stored in grain seeds.) In about 80 to 90 percent of celiac cases, the patient’s inflammatory response to gluten – which leads to the destruction of the intestinal lining if gluten is consumed frequently – arises because they are carriers of the HLA-DQ2.5 gene. This gene creates a recognition protein that instructs T-cells to flag harmless gluten peptides as dangerous.
The vaccine will not work for individuals with non-HLA-DQ2.5-mediated gluten sensitivity.
“The initiation of our Nexvax2 Phase 2 trial is significant for patients who suffer from celiac disease, a condition affecting approximately 1% of the global population,” Leslie Williams, CEO of ImmusanT, the company behind Nexvax2, said in a statement earlier this year. “This trial is designed to demonstrate protection against inadvertent exposure to gluten, but the ultimate goal is to develop Nexvax2 as a treatment that will allow patients to return to an unrestricted diet.”
According to Dr Jason Tye-Din, a gastroenterologist at the Royal Melbourne Hospital and head of celiac research at the Walter and Eliza Hall Institute, the vaccine is expected to work for the majority of patients with the genetic form of celiac disease. Dr Tye-Din, who will lead the Australian portion of the trial, has been involved with Nexvax2 since the beginning. He and Dr Bob Anderson, now chief scientific officer for ImmusanT, led the team that first identified the immune-triggering peptides in 2003.
ImmusanT researchers hope to enroll 150 celiac patients across the three countries. Participants will receive 32 total injections of Nexvax2 or placebo, given at twice-weekly intervals, then undergo masked gluten food challenges (meaning they won’t know whether or not gluten is present in the food items). The company reported that the first patient joined the trial and began injections in late September. As of now, most of the 40 study sites are actively recruiting more participants or will begin to do so soon.
“This trial is important in establishing clinical proof-of-concept for a treatment that would provide benefit beyond that of the gluten-free diet,” Dr Tye-Din stated. “The gluten-free diet is the only current treatment for celiac disease, but it is onerous, complex and not always effective. Even the most diligent patients can suffer the adverse effects of accidental exposure.”
"A successful therapy that can restore normal gluten tolerance would revolutionize celiac disease management,” he said in a different release.
Per the ImmusanT website, treatment with Nexvax2 will involve multiple doses to gradually acclimate T-cells to gluten peptides. During which time, the inflammation and tissue damage in the gut may heal, alleviating the disease’s symptoms. Ideally, the individual could then consume gluten in small amounts or freely without an immune response. Periodic boosters will be needed to maintain prolonged gluten tolerance.