TL1A inhibitor tulisokibart shows potential in UC

In the extension period of the phase 2 ARTEMIS-UC study, tulisokibart displayed sustained improvements in clinical and endoscopic outcomes in patients with moderately to severely active ulcerative colitis (UC). A phase 3 programme has been launched to assess this agent in a larger population.

“We know that tumour necrosis factor-like cytokine 1A [TL1A] is a mediator of inflammation and fibrosis,” mentioned Dr Christopher Ma (University of Calgary, Canada) [1–3]. “Tulisokibart is a humanised monoclonal antibody that binds to both soluble and membrane-associated TL1A with high affinity and specificity” [3,4].

In the induction part of the phase 2 ARTEMIS-UC trial (NCT04996797), the TL1A inhibitor tulisokibart was associated with better clinical, endoscopic, and patient-reported outcomes compared with placebo in participants with moderately to severely active UC [3,5]. During the 12-week induction phase, participants in the active arm (n=68) received 1,000 mg of tulisokibart intravenously administered on day 1, followed by 500 mg every 4 weeks. Responders were eligible to enter the open-label extension phase, where they received tulisokibart maintenance therapy for up to 170 weeks. The responders (n=47) were randomised 1:1 to tulisokibart 250 mg or to tulisokibart 100 mg every 4 weeks. Dr Ma presented the findings after 50 weeks of follow-up [3].

The clinical remission rate was 32% in the 100 mg arm and 48% in the 250 mg arm. Endoscopic improvement was observed in 36% and 48% of the participants in the 100 mg arm and 250 mg arm, respectively. Furthermore, the clinical response rates were 59% and 68% for the low-dose and high-dose arms. Histologic improvement was documented in 67% of participants receiving 100 mg and 70% in those receiving 250 mg (see Figure).

Figure: Maintenance of responses for symptomatic and histologic outcomes in patients with UC at week 50 [3]



“The severe adverse event rates were low, with 10% (n=3) of the participants in the 100 mg arm and 3% (n=1) of the participants in the 250 mg arm,” expressed Dr Ma. No acute infusion reactions or peri-infusion reactions were reported. The infection rate was 37% in the 100 mg arm and 46% in the 250 mg arm. “These were, however, predominantly upper respiratory infections. We did not see any serious infections or infections related to systemic immunosuppression, such as herpes zoster,” clarified Dr Ma.

Altogether, tulisokibart showed encouraging long-term efficacy data and favourable safety results in the current phase 2 study, supporting the need for further investigation in phase 3 studies.

1. 
   
   1. Valatas V, et al. Front Immunol. 2019;10:583.
   2. Kokkotis G and Bamias G. Expert Rev Clin Immunol. 2022;18(6):551-555.
   3. Ma C, et al. Long-term efficacy and safety of tulisokibart in patients with ulcerative colitis: results from the open-label extension period of the phase 2 ARTEMIS-UC study. OP194, UEG Week 2024, 12–15 October, Vienna, Austria.
   4. Fransson J, et al. 15^th annual PEGS Europe 2023 Protein & Engineering Summit, 14–16 November, Lisbon, Portugal.
   5. Sands BE, et al. J Crohns Colitis. 2023;17:i56-i59.

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Posted on 28 November 2024