Credit: Sebastian Kaulitzki | stock.adobe.com
Tulisokibart (Merck) showed superior efficacy to placebo in achieving clinical remission in patients with moderately to severely active ulcerative colitis (UC), according to data from the proof-of-concept Phase II ARTEMIS-UC trial (NCT04996797) published by The New England Journal of Medicine.1,2 The investigational humanized monoclonal antibody is currently in development to treat immune-mediated inflammatory diseases such as Crohn disease and systemic sclerosis-associated interstitial lung disease, as well as UC. A pair of Phase III trials—ATLAS-UC (NCT06052059) and ARES-CD (NCT06430801) are currently evaluating the efficacy and safety of tulisokibart in patients with UC and Crohn disease, respectively.
“We are encouraged by the new maintenance data for tulisokibart in ulcerative colitis and Crohn’s disease, which shows the potential of this novel approach to help patients achieve long-term clinical remission,” said Aileen Pangan, MD, vice president, global clinical development, Merck Research Laboratories, in a press release. “Many patients with inflammatory bowel disease do not achieve their treatment goals despite available therapies. There is still a need for additional treatment options to enable patients to manage the challenging symptoms of ulcerative colitis and Crohn’s disease.”3
The multicenter, double-blind, placebo-controlled ARTEMIS-UC trial enrolled patients with glucocorticoid dependence or who failed conventional or advanced therapies for UC. Patients were randomly assigned to receive intravenous tulisokibart at a dose of 1000 mg on day one and 500 mg at weeks two, six, and 10, or placebo.
Cohort one enrolled 135 patients regardless of testing results to show their likelihood of response, whereas cohort two enrolled 43 patients who tested positive for likelihood of response, with the trial’s primary analysis conducted in cohort one. The trial’s primary endpoint was clinical remission at week 12.
A significantly greater proportion of patients in cohort one administered tulisokibart achieved clinical remission compared with placebo (26% vs. 1%; difference, 25 percentage points; 95% confidence interval [CI], 14 to 37; P<0.001). Further, 75 patients testing positive for likelihood of response were randomized across both cohorts. Combined patients from both cohorts testing positive for likelihood of response showed a higher rate of clinical remission in those administered tulisokibart than in those administered placebo (32% vs. 11%; difference, 21 percentage points; 95% CI, 2 to 38; P=0.02).
“A significant benefit of tulisokibart as compared with placebo was also observed for all ranked secondary end points for cohort 1,” the study authors wrote. “Specifically, more patients in the tulisokibart group than in the placebo group had endoscopic improvement (37% vs. 6%; difference, 31 percentage points; 95% CI, 17 to 43; P<0.001) and a clinical response (66% vs. 22%; difference, 44 percentage points; 95% CI, 27 to 57; P<0.001).”1
In terms of safety, reports of adverse events (AEs) was similar across both the tulisokibart and placebo cohorts, with most AEs deemed mild to moderate in severity. Serious AEs were reported by one patient in the tulisokibart cohort and seven patients in the placebo cohort. COVID-19 was the only AE reported by more than 5% of patients in either cohort, with worsening of UC reported more frequently in the placebo cohort.
Investigators noted that further research is needed to evaluate the diagnostic potential and long-term safety of tulisokibart with larger numbers of patients and observations across longer durations.
“After 12 weeks of induction therapy, a significant difference in the incidence of clinical remission was observed in favor of tulisokibart as compared with placebo among patients in cohort 1. A consistent benefit was also shown for all prespecified ranked secondary end points in cohort 1, including endoscopic improvement, clinical response, histologic improvement, combined endoscopic and histologic improvement, and symptomatic remission,” the study authors concluded.1
They added, “Collectively, these observations of both objective and patient-reported efficacy end points provide evidence that TL1A blockade is a new mechanism of action for the treatment of moderately to severely active ulcerative colitis, irrespective of previous exposure to advanced therapy.”1
References
1. Sands B., et al. Phase 2 Trial of Anti-TL1A Monoclonal Antibody Tulisokibart for Ulcerative Colitis. Published September 25, 2024. N Engl J Med 2024;391:1119-1129 DOI: 10.1056/NEJMoa2314076. Vol. 391 No. 12.
2. A Phase 2 Safety and Efficacy Study of Tulisokibart (MK-7240/PRA023) in Subjects With Moderately to Severely Active Ulcerative Colitis (MK-7240-005) (ARTEMIS-UC). ClinicalTrials.gov. Updated July 30, 2024. Accessed October 2, 2024. https://clinicaltrials.gov/study/NCT04996797
3. Merck to Present New Long-Term Data for Tulisokibart (MK-7240), an Investigational Anti-TL1A Monoclonal Antibody, in Inflammatory Bowel Disease at UEG Week 2024. News release. Merck. September 26, 2024. Accessed October 2, 2024. https://www.merck.com/news/merck-to-present-new-long-term-data-for-tulisokibart-mk-7240-an-investigational-anti-tl1a-monoclonal-antibody-in-inflammatory-bowel-disease-at-ueg-week-2024/