ARTEMIS-UC: New kid in town for UC

In a phase 2 trial, induction therapy with the investigational agent MK-7240 was associated with higher clinical remission rates than placebo in participants with moderately to severely active ulcerative colitis (UC). According to the authors, a phase 3 study will be initiated to confirm these results.

MK-7240 is an investigational monoclonal antibody inhibiting tumour necrosis factor-like cytokine 1A (TL1A)-mediated signalling. TL1A is an upstream regulator of pro-inflammatory cytokines and fibrosis signals. The phase 2 ARTEMIS-UC trial (NCT04996797) randomised 135 participants with moderately to severely active UC 1:1 to placebo or MK-7240 [1]. Participants in the active arm received 1,000 mg of this agent intravenously on day 1 and 500 mg every 4 weeks, starting from week 2. The primary endpoint was clinical remission per modified Mayo score (MMS) at week 12, defined as endoscopic subscore of 0 or 1, rectal bleeding subscore (RBS) of 0, and stool frequency subscore of 0 or 1 and not greater than baseline. Secondary endpoints included clinical response (defined as a decrease from baseline in the MMS of ≥30% and ≥2 points, and a decrease of ≥1 point in the RBS or an RBS ≤1), endoscopic improvement (i.e. endoscopy subscore ≤1 with no friability), and mucosal healing (Geboes score ≤2B.1 and endoscopy subscore ≤1). Dr Bruce Sands (Icahn School of Medicine at Mount Sinai, NY, USA) presented the main findings.

The primary endpoint was met, with 26.5% and 1.5% of the participants achieving clinical remission at week 12, favouring the active arm over the placebo arm (95% CI 13.9–36.6; P<0.0001). In addition, all secondary efficacy endpoints showed improvements with MK-7240 compared with placebo, including endoscopic improvement (36.8% vs 6.0%; 95% CI 17.4–43.2; P<0.0001), clinical response (66.2% vs 22.4%; 95% CI 27.4–56.9; P<0.0001), mucosal healing (30.8% vs 3.5%; 95% CI 14.3–39.6; P<0.0001), and inflammatory bowel disease questionnaire (IBDQ) response (82.4% vs 49.3%; 95% CI 17.2–46.8; P<0.0001). Moreover, the results appeared to be consistent in advanced therapy-experienced participants.

Adverse events (AEs) were observed in 40.3% and 41.2% of the participants in the placebo arm and experimental arm, respectively. Serious AEs were reported in 7.5% and 0.0% of the participants, numerically favouring the active arm over the placebo arm. Finally, the rates of infections and infestations were comparable, with 16.4% in the placebo arm and 14.7% in the MK-7240 arm.

In conclusion, MK-7240 showed encouraging efficacy and safety results in participants with moderately to severely active UC in this phase 2 study, instigating the launch of a phase 3 trial.

1. 
   
   1. Sands BE, et al. A phase 2, randomised, double-blind, placebo-controlled trial of PRA023 (MK-7240) as induction therapy in patients with moderately to severely active ulcerative colitis: ARTEMIS-UC, Cohort 1. OP102, UEG Week 2023, 14–17 October, Copenhagen, Denmark.

Copyright ©2023 Medicom Medical Publishers



Posted on 7 December, 20238 April, 2024