(P036) TREATMENT OF MODERATELY TO SEVERELY ACTIVE ULCERATIVE COLITIS WITH RO7790121 DEMONSTRATES EARLY CLINICAL RESPONSE AND SYMPTOM IMPROVEMENT – RESULTS FROM THE PHASE 2B TUSCANY-2 TRIAL (Posters of Distinction)

Tumor necrosis factor-like ligand 1A (TL1A) is upregulated in IBD, promoting inflammation and intestinal fibrosis, and is a potential therapeutic target. RO7790121 (previously PF-06480605, RVT-3101), an anti-TL1A antibody, was effective and well tolerated in the phase 2a TUSCANY trial. We report results from TUSCANY-2, a phase 2b, randomized, double-blind, treat-through, dose-ranging study evaluating efficacy and safety of subcutaneous (SC) doses of RO7790121 in patients (pts) with moderately to severely active ulcerative colitis (UC).

Pts aged 18–75 with moderately to severely active UC were randomized to receive RO7790121 SC 50mg, 150mg, 450mg or matched placebo (PBO) monthly during the 12-week induction period, and RO7790121 SC 50mg, 150mg or 450mg monthly during the 40-week treat-through maintenance period. The exploratory endpoint of clinical response, defined as a ≥2-point and ≥30% decrease from baseline in modified Mayo Score (mMS) along with a decrease from baseline in rectal bleeding subscore (RBS) of ≥1 point or absolute RBS 0 or 1, was assessed at Weeks 14 and 56. Change from baseline in the patient reported outcomes (PROs) of rectal bleeding (RB), stool frequency (SF) and partial mMS (RB+SF) over time were also evaluated. Safety was assessed throughout the study.

Overall, 245 pts received ≥1 dose of RO7790121. The proportion of pts at Week 14 who achieved clinical response was 68.1%, 61.7%, and 69.3% in the RO7790121 50mg, 150mg, and 450mg arms, respectively, vs 44.2% in the PBO arm. Improvements in clinical response were sustained at Week 56 (Table). Throughout induction, and as early as Week 2, decreases in SF, RB and partial mMS PROs (RB+SF) were greater across all RO7790121 treatment groups, compared with PBO (Figure). Improvements in SF and RB were sustained throughout the maintenance period (Table). In total, 47.8% (117/245) of pts reported ≥1 treatment-emergent adverse event (TEAE), the most common (reported in ≥5% of pts in any treatment group) during induction were anemia (PBO: 4/45 [8.9%]; 150mg: 5/62 [8.1%]), UC (50mg: 3/47 [6.4%]), nausea (50mg: 3/47 [6.4%]), fatigue (450mg: 5/91 [5.5%]), pyrexia (450mg: 5/91 [5.5%]), urinary tract infection (50mg: 3/47 [6.4%]), and headache (450mg: 9/91 [9.9%]). During induction, 10 pts experienced serious TEAEs (PBO: 4; 50mg: 3; 450mg: 3); two were treatment related (PBO: 1; 450mg: 1). No pts discontinued the study due to TEAEs and a similar safety profile was observed during the maintenance period.

A higher proportion of pts receiving RO7790121 achieved clinical response at Week 14 compared with PBO. This was accompanied by greater and more rapid improvements in RB and SF in pts treated with RO7790121. These data indicate a favorable benefit/risk profile for RO7790121 including early symptom improvements. Phase 3 studies (NCT06589986, NCT06588855) are ongoing to confirm these findings.