Novel TL1A inhibitor achieves high rates at stringent endpoints in UC

Treatment with the investigational TNF ligand 1A (TL1A) inhibitor RO7790121 resulted in promising histologic improvement, histologic remission, and histologic-endoscopic remission rates compared with placebo in participants with ulcerative colitis (UC) in the phase 2 TUSCANY-2 trial.

The phase 2 TUSCANY-2 study (NCT04090411) previously showed that RO7790121 induction therapy was efficacious in terms of clinical remission among participants with moderately to severely active UC [1]. The trial randomised 245 participants to placebo (n=45) or RO7790121 50 mg (n=47), 150 mg (n=62), or 450 mg (n=91), subcutaneously administered every 4 weeks. After 14 weeks, all participants received active therapy during the maintenance phase. Prof. Vipul Jairath (Western University, Canada) presented data on histologic and histologic-endoscopic endpoints at week 14 and week 56, which were performed per non-responder imputation [2].

At week 14, histologic improvement was documented in 40.0%, 39.6%, and 32.9% of the participants in the 50 mg, 150 mg, and 450 mg arms, respectively, whereas only 12.2% of the participants on placebo reached this endpoint. The corresponding rates for histologic remission at week 14 were 35.0%, 35.8%, 30.5%, and 4.9%. “These rates were sustained at week 56,” Prof. Jairath pointed out. Histologic-endoscopic mucosal remission was reported for 27.5%, 28.3%, and 23.2% of the participants in the respective active arms, whereas only 4.9% on placebo achieved this stringent endpoint. These 14-week results were sustained at week 56 (see Figure).

Figure: Histologic improvement and remission rates at week 14 were sustained at week 56 in participants treated with RO7790121 [2]



Finally, RO7790121 was well-tolerated, with only 1 serious treatment-related adverse event (TRAE) reported in the 450 mg arm during the induction phase and 1 serious TRAE observed during the maintenance phase in the 450 mg arm.

“In addition to the previously presented clinical evidence from TUSCANY-2, the histologic and histologic-endoscopic outcomes highlight that the TL1A inhibitor RO7790121 is a novel promising therapeutic for the management of patients with UC,” concluded Prof. Jairath.

1. Danese S, et al. OP079, UEG Week 2024, 12–15 October, Vienna, Austria.
2. Jairath V, et al. Treatment with RO7790121 induces and maintains histologic and histologic-endoscopic improvement and remission in moderately to severely active ulcerative colitis: results from TUSCANY-2. OP39, 20th Congress of ECCO, 19–22 February 2025, Berlin, Germany.

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Posted on 8 April 20258 April 2025