OP39 Treatment with RO7790121 induces and maintains histologic and histologic-endoscopic improvement and remission in moderately to severely active ulcerative colitis – Results from TUSCANY-2
Authors: Jairath V , Allegretti J R , Yarur A , Danese S , Schreiber S , Peyrin-Biroulet L , Kierkus J , Leong R W , Vincent M S , Banerjee A , Chandra D E , Peeva E , Neelakantan S , Hung K E , Bojic D , Lasch K , Schiffman C , Feagan B 
Published: January 2025

Abstract

Background
Tumor necrosis factor-like ligand 1A (TL1A) is upregulated in inflammatory bowel disease, promoting inflammation and intestinal fibrosis. Targeting TL1A with the anti-TL1A antibody RO7790121 showed significant endoscopic improvement and favorable safety in the phase IIa TUSCANY trial1 and the subsequent phase IIb TUSCANY-2 trial (NCT04090411) in patients (pts) with moderately to severely active ulcerative colitis (UC). Here we report histologic and endoscopic improvement and remission data from the phase IIb TUSCANY-2.

Methods
Pts aged 18–75 years with moderately to severely active UC (total Mayo score ≥6, endoscopic subscore [ES] ≥2) were enrolled in this multicenter, randomized, double-blind, treat-through, dose-ranging study. Pts were randomized to receive subcutaneous (SC) RO7790121 50mg, 150mg, 450mg or matched placebo (PBO) monthly during the 12-week induction period, and SC RO7790121 50mg, 150mg or 450mg monthly during the 40-week, treat-through maintenance period. Histologic endpoints included histologic improvement (Geboes score [GS] ≤3.1) and remission (GS &lt;2B.1), as well as histologic-endoscopic mucosal improvement (GS ≤3.1 and ES ≤1) and remission (GS &lt;2B.1 and ES ≤1), assessed at Weeks 14 and 56.

Results
A total of 245 pts received ≥1 dose of RO7790121 or PBO; 228 pts completed the induction; 224 entered the maintenance period and 178 completed the maintenance period. At Week 14, the proportions of pts with histologic improvement (using Geboes histology score) were 40.0%, 39.6% and 32.9% with RO7790121 50mg, 150mg and 450mg, respectively, vs 12.2% with PBO, which were sustained through Week 56. Greater proportions of pts with histologic remission were also observed with any RO7790121 dose vs PBO at Week 14, sustained through Week 56 (Table). Additionally, 30.0%, 32.1% and 25.6% of pts treated with RO7790121 50mg, 150mg and 450mg, respectively, vs 4.9% with PBO experienced histologic-endoscopic mucosal improvement, which was sustained through Week 56. Greater histologic-endoscopic mucosal remission was also observed at any RO7790121 dose vs PBO at Week 14 and sustained through Week 56 (Table). Across the various endpoints, there was no apparent dose response.

Conclusion
Overall, higher rates of histologic improvement and remission were observed in pts treated with RO7790121 during induction, compared with PBO, and sustained through Week 56. Similarly, a higher proportion of pts treated with RO7790121 achieved histologic-endoscopic mucosal improvement and remission, sustained through Week 56. RO7790121 is currently being investigated in phase III studies (NCT06589986 and NCT06588855).

References
1.Danese S, Klopocka M, Scherl EJ, et al. Anti-TL1A antibody PF-06480605 safety and efficacy for ulcerative colitis: A phase 2a single-arm study. Clin Gastroenterol Hepatol. 2021;19(11):2324-2332.e6. http://doi.org/10.1016/j.cgh.2021.06.011