TEV '408 Meets Primary Endpoint in Celiac Trial

TEV '408, an investigational anti-interleukin-15 (IL-15) monoclonal antibody, met its primary endpoint, with statistically significant and clinically meaningful prevention of gluten-induced intestinal damage versus placebo at week 8.

Teva Pharmaceutical Industries Ltd announced the positive topline results from an ongoing phase 2a study in adults with celiac disease. There are currently no US Food and Drug Administration (FDA)-approved therapies for celiac disease, and a strict, lifelong gluten-free diet remains the standard of care.

"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, MD, PhD, Executive Vice President, Global R&D and Chief Medical Officer at Teva, in a statement.

What Is TEV '408's Mechanism of Action?

TEV '408's primary mechanism of action is to bind and block the activity of IL-15, a key inflammatory cytokine that plays a central role in tissue inflammation and the destruction of healthy cells in immune conditions. By neutralizing IL-15 signaling, the therapeutic is intended to directly target the immune-mediated destruction underlying multiple chronic inflammatory diseases.

In celiac disease, TEV '408 blocks gluten-induced IL-15 signaling, lowering the density of intraepithelial lymphocytes (IELs) and preventing the characteristic structural damage, such as villous atrophy, to the small intestine.

The therapy has a long half-life and is designed as a subcutaneous injection given once every 12 weeks.

Design and Results of the Ongoing Phase 2a Study

The ongoing randomized, placebo-controlled study enrolled 50 adult participants with celiac disease on a gluten-free diet (GFD) with minimal intestinal damage at baseline, as measured by villous height-to-crypt depth ratio (Vh:Cd ≥2.0) and symptoms. Two weeks after receiving a single dose of TEV '408, participants began a 6-week daily gluten challenge (GC). The study assessed biopsy-based measures of intestinal damage and inflammation along with patient-reported symptoms.

By week 8, TEV '408:

• Showed statistically significant and clinically meaningful prevention of gluten-induced intestinal damage versus placebo, as measured by the trial's primary endpoint of Vh:Cd ratio, with a least squares (LS) mean change from baseline of -0.43 compared with -0.88 for placebo (treatment difference of 0.45, 95% CI: 0.06-0.84, p<0.05)
• Showed a favorable effect on intestinal inflammation as measured by density of IELs compared with placebo; the LS mean change from baseline in IEL density was an increase of 27.60 for placebo compared with 0.37 for TEV '408-treated participants (treatment difference of -27.23, 95% CI: -39.67 to -14.79)
• Demonstrated lower gastrointestinal symptom scores versus placebo, as assessed using the Celiac Disease Symptom Diary (CDSD), a patient-reported outcome (PRO)
• Was well-tolerated, with no emerging safety signals

Additional analyses from the ongoing phase 2a study are underway.

"These results underscore the potential to move beyond managing gluten exposure and address celiac disease at its biological source," Hughes said in a statement. "They also strengthen our confidence in targeting the IL-15 pathway as an approach to reducing immune-driven intestinal damage."

References

1. Teva Pharmaceutical. Teva Announces Positive Topline Results from Phase 2a Study in Celiac Disease for Its Anti-IL-15 Antibody, Further Validating Its Pipeline-in-a-Product Potential. Tevapharm.com. September 2, 2026. Accessed September 2, 2026. https://www.tevapharm.com/news-and-media/latest-news/teva-announces-positive-topline-results-from-phase-2a-study-in-celiac-disease-for-its-anti-il-15-antibody/

2. Schnir V, Rigby M, Calota MR, et al. Su1326 Developing TEV-53408 for the Treatment of Celiac Disease: Summary of Preliminary Results From the First in Human Phase 1 Study in Healthy Volunteers. Gastroenterology. 2024;166(5):S-730. doi:10.1016/s0016-5085(24)02155-3