A single subcutaneous dose of TEV-'408, Teva Pharmaceutical Industries' (NYSE: TEVA) investigational anti-interleukin-15 monoclonal antibody, significantly attenuated gluten-induced intestinal damage compared with placebo in a Phase IIa trial in adults with celiac disease — an indication with no approved pharmacotherapy.
The randomized, placebo-controlled study enrolled 50 adults with celiac disease on a gluten-free diet (GFD) who had minimal intestinal damage at baseline. Two weeks after receiving a single dose of TEV-'408, participants began a six-week daily gluten challenge. At week 8, the primary endpoint — villous height-to-crypt depth (Vh) ratio — showed a least squares mean change from baseline of −0.43 for TEV-'408 versus −0.88 for placebo, representing a treatment difference of 0.45 (95% CI: 0.06, 0.84; p<0.05).
Intraepithelial lymphocyte (IEL) density, a measure of intestinal inflammation, increased by 27.60 in the placebo arm versus 0.37 in the TEV-'408 arm. Patient-reported gastrointestinal symptom scores, assessed using the Celiac Disease Symptom Diary, were also lower in the treatment group. No emerging safety signals were observed to date.
TEV-'408 blocks IL-15, a cytokine involved in the innate and adaptive immune responses underlying celiac disease, including the activation of intraepithelial lymphocytes that contribute to villous damage following gluten exposure. By targeting this immune pathway rather than gluten itself, TEV-'408 is designed to interrupt a downstream driver of intestinal inflammation and tissue damage.
Celiac disease affects approximately 1% of the global population, yet a GFD remains the sole standard of care. Even with careful adherence, patients can experience persistent symptoms and ongoing intestinal inflammation or damage, including from inadvertent gluten exposure. No drug has received regulatory approval for the indication. The US FDA granted TEV-'408 Fast Track designation for celiac disease in May 2025.
The celiac data arrive two months after Teva reported Phase Ib vitiligo results for TEV-'408, in which 42% of evaluable patients achieved F-VASI50 at week 24 following two doses, prompting advancement into a Phase IIb vitiligo study planned for Q4 2026. Both indications involve IL-15-mediated immune mechanisms affecting tissue-resident cells, giving Teva a rationale for pursuing the molecule across multiple autoimmune diseases. Royalty Pharma committed up to USD 500 million in January 2026 to accelerate TEV-'408's clinical development.
The celiac pipeline remains relatively early-stage, with no approved pharmacotherapy. Takeda's TAK-227/ZED1227, an oral transglutaminase 2 inhibitor, is in Phase IIb development, while ZymagenX is preparing the oral gluten-degrading enzyme latiglutenase for Phase III development. Latiglutenase targets gluten within the gastrointestinal tract, potentially reducing the consequences of inadvertent exposure without directly modifying the underlying immune response. TEV-'408 instead acts downstream of antigen exposure on an immune pathway involved in intestinal damage. Its planned quarterly subcutaneous dosing profile, if supported in later-stage celiac studies, could also differentiate it from daily oral approaches.
The most direct competitive pressure in the IL-15 pathway comes from argenx's FB102, an anti-CD122 antibody added through the company's USD 2.2 billion acquisition of Forte Biosciences, which was completed in August 2026. FB102 targets CD122, the shared beta subunit of the IL-2 and IL-15 receptors, thereby modulating signaling through both cytokine pathways. Forte reported positive Phase Ib celiac disease data in June 2025, and a Phase II celiac study is underway, with data expected in H2 2026. The mechanistic overlap between TEV-'408 and FB102 creates a potentially informative test of selective IL-15 blockade against broader CD122-mediated inhibition of IL-2 and IL-15 signaling.
Teva said additional analyses from the ongoing Phase IIa study are underway and plans to present further data at a future scientific meeting.
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