S13 RO7790121 as Treatment for Moderately to Severely Active Ulcerative Colitis: Efficacy and Health-Related Quality of Life Improvements: Results from the Phase IIb TUSCANY-2 Trial

Background: Following promising results from a phase IIa study, the global, randomized, double-blind, placebo-controlled, dose-ranging phase IIb TUSCANY-2 trial (NCT04090411) aimed to evaluate the efficacy and safety of the anti-tumor necrosis factor-like ligand 1A- antibody RO7790121 in patients with ulcerative colitis (UC). As reported previously at UEG week 2024 and ACG 2024, adult patients with moderately to severely active UC (total Mayo Score [tMS]–12, endoscopic subscore ≥2) who had failed ≥1 prior conventional/advanced treatment were randomized to receive RO7790121 subcutaneously (SC) 50 mg, 150 mg, 450 mg, or placebo monthly during the 12-week induction period and RO7790121 SC 50 mg, 150 mg, or 450 mg monthly during the treat-through, 40-week maintenance period. The primary endpoint (clinical remission by tMS) was assessed at week 14 in the intent-to-treat population and the secondary endpoints (clinical remission by modified Mayo score [mMS], which is more aligned to updated FDA guidance; endoscopic improvement) were assessed at weeks 14 and 56 in the induction and maintenance intent-to-treat population, respectively. At week 14, clinical remission by tMS was achieved in 25.5%, 23.3% and 23.9% of participants in the RO7790121 50-mg, 150-mg, 450-mg arms, respectively vs 11.6% receiving placebo (p>0.05). The proportion of patients showing clinical remission by mMS at week 14 was 29.8%, 35.0% and 31.8% in the RO7790121 50-mg, 150-mg, 450-mg arms, respectively vs 11.6% in placebo (nominal P< 0.05). Improvements in clinical remission were sustained throughout maintenance. At week 14, 40.4%, 38.3% and 40.9% of patients in the RO7790121 50-mg, 150-mg, 450-mg arms, respectively vs 18.6% receiving placebo demonstrated endoscopic improvement, sustained through week 56. Here, we report effect of RO7790121 on health-related quality of life (HRQoL) in patients with UC. Methods: Patient-reported HRQoL during induction and maintenance was assessed using the IBD Questionnaire (IBDQ) at weeks 4, 8, 12, 14, 24 and 52. Safety was assessed throughout. Results: Overall, 245 patients were randomized and treated; 228 completed the induction; 224 entered the maintenance period. Improvements in total IBDQ score from baseline were observed across all RO7790121 arms from week 4 (mean change from baseline 33.82 [90% confidence interval (CI) 26.18–41.46], 35.76 [29.13–42.4] and 35.87 [30.38–41.35] in the RO7790121 50-mg, 150-mg, 450-mg arms, respectively vs 16.78 [9.01–24.55] with placebo), sustained up to week 52. Improvements in fatigue, abdominal pain and bloating were also observed from week 4, sustained throughout induction and maintenance. During induction, 47.8% (117/245) of patients reported ≥1 treatment-emergent adverse event (TEAE). The most common TEAEs during induction (occurring in ≥5% patients overall) were anemia (5.3%) and headache (5.3%). In the induction period, 10 patients experienced serious TEAEs (placebo=4; 50 mg=3; 150 mg=0; 450 mg=3); 2 treatment-related (placebo=1; 450 mg=1). No patients discontinued the study due to TEAEs. A generally similar safety profile was observed during maintenance. Conclusions: Data from the phase IIb TUSCANY-2 study suggest that RO7790121 leads to meaningful improvements in clinical and endoscopic endpoints, as well as in HRQoL of patients with moderately to severely active UC, with a favorable risk/benefit profile. A confirmatory phase III study is currently underway.

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