Teva Pharmaceutical Industries (TEVA) Study result summary

Study Background and Rationale

• Celiac disease affects 1% of the US, EU, and global population, with about half of patients experiencing persistent symptoms despite a gluten-free diet and no approved therapies.

• IL-15 is a key cytokine in celiac disease pathogenesis, driving gut inflammation, villous atrophy, and crypt hyperplasia.

• TEV-408 is an anti-IL-15 antibody designed for high potency, long half-life, and strong preclinical efficacy, aiming to protect intestinal architecture and address unmet needs.

• Preclinical studies in primates and phase I data in humans showed robust disease modification, safety, and suppression of gut damage markers.

• The program targets a significant unmet need, as managing celiac disease imposes a daily burden and no pharmacotherapies exist.

Study Design and Execution

• Phase IIa was a randomized, double-blind, placebo-controlled study in 50 adults with biopsy-confirmed celiac disease on a gluten-free diet.

• Participants received a single subcutaneous dose of TEV-408 or placebo, followed by a six-week daily gluten challenge.

• The primary endpoint was prevention of gluten-induced intestinal damage, measured by villous height-to-crypt depth (Vh:Cd) ratio at week 8.

• Secondary endpoints included intraepithelial lymphocyte (IEL) counts, patient-reported GI symptoms, and biomarkers.

• The study was well-executed, with most patients completing the protocol and balanced arms.

Key Efficacy and Safety Results

• TEV-408 showed statistically and clinically significant prevention of gluten-induced intestinal damage, with a Vh:Cd ratio difference of 0.45 (p<0.05) versus placebo.

• Intraepithelial lymphocyte counts remained stable or decreased with TEV-408, while placebo saw a significant increase (treatment difference -27.23).

• Lower GI symptom scores and favorable trends in patient-reported outcomes were observed with TEV-408.

• TEV-408 was well-tolerated, with a favorable safety profile and no emerging safety signals across multiple studies.

• Single-dose efficacy over three months and quarterly dosing potential highlight the compound’s potency and convenience.