Teva Pharmaceutical Industries reported positive topline results from an ongoing Phase 2a study of TEV ‘408, an investigational anti-interleukin-15 (IL-15) monoclonal antibody for adults with celiac disease.
The study met its primary endpoint, showing that a single dose of TEV ‘408 produced a statistically significant and clinically meaningful reduction in gluten-induced intestinal damage compared with placebo at week 8. The treatment was also well tolerated, with no safety signals reported to date.
“A strict gluten-free diet has long been the only option for people living with celiac disease. Yet, even with strict adherence to a gluten-free diet, many continue to experience symptoms, intestinal damage and a significant impact on their daily lives,” said Eric Hughes, Executive Vice President, Global R&D and Chief Medical Officer at Teva.
“These results underscore the potential to move beyond managing gluten exposure and address celiac disease at its biological source. They also strengthen our confidence in targeting the IL-15 pathway as an approach to reducing immune-driven intestinal damage.”
The randomized, placebo-controlled Phase 2a trial enrolled 50 adults with celiac disease who were following a gluten-free diet and had minimal intestinal damage and symptoms at baseline.
Participants received a single dose of TEV ‘408 and, two weeks later, began a six-week daily gluten challenge. Researchers assessed intestinal damage and inflammation through biopsies, as well as patient-reported symptoms.
The treatment significantly reduced gluten-induced intestinal damage, measured by the villous height-to-crypt depth (Vh:Cd) ratio. The least squares mean change from baseline was -0.43 with TEV ‘408 versus -0.88 with placebo, representing a treatment difference of 0.45.
TEV ‘408 was associated with a substantially smaller increase in intraepithelial lymphocyte (IEL) density. The least squares mean change was 0.37 with TEV ‘408 versus 27.60 with placebo, a treatment difference of -27.23.
Participants receiving TEV ‘408 reported lower GI symptom scores than those receiving placebo, based on the Celiac Disease Symptom Diary (CDSD).
The findings point to the potential of targeting the IL-15 pathway, a key driver of immune-mediated intestinal injury in celiac disease, rather than relying solely on avoidance of gluten exposure.
