Safety and efficacy of the anti-TL1A monoclonal antibody tulisokibart for Crohn's disease: a phase 2a induction trial

Background

TNF-like cytokine 1A (TL1A) is a key mediator of inflammation and fibrosis. The efficacy and safety of the anti-TL1A monoclonal antibody tulisokibart as induction treatment was assessed in adults with moderately to severely active Crohn's disease with a history of insufficient response, loss of response, or intolerance to conventional or approved biological therapies.

Methods

In the phase 2a, multicentre, open-label APOLLO-CD study, participants aged 18 years or older with moderately to severely active Crohn's disease, as defined by a Crohn's Disease Activity Index (CDAI) of 220–450 and a Simple Endoscopy Score for Crohn's Disease (SES-CD) of at least 6 for ileocolonic or colonic disease or at least 4 for isolated ileal disease, received intravenous tulisokibart (1000 mg on day 1 and 500 mg at weeks 2, 6, and 10). This Article reports the results of the primary analysis of the induction period. The primary endpoints were safety and the proportion of participants with endoscopic response at week 12, defined as a decrease in SES-CD of at least 50% from baseline. Safety was analysed in all participants treated with tulisokibart, and endoscopic response was analysed in the per-protocol analysis set, which included all participants treated with tulisokibart with baseline CDAI and SES-CD scores, except those with prespecified important protocol deviations. This trial is registered with ClinicalTrials.gov (NCT05013905) and is closed for recruitment; an open-label extension is ongoing.

Findings

Of 101 participants screened for eligibility, 55 eligible participants were enrolled and received tulisokibart. The mean age of participants was 39·1 years (SD 15·7), 34 (62%) were male, 21 (38%) were female, and 39 (71%) had received previous biological therapy. At week 12, endoscopic response was observed in 13 (26·0% [95% CI 15·9–39·6]) of 50 participants receiving tulisokibart in the per-protocol analysis set. Adverse events occurred in 43 (78%) of 55 participants, with most adverse events being mild to moderate in severity. The most frequently occurring adverse events (≥5% of participants) were COVID-19 (six [11%] participants), urinary tract infection (five [9%]), Crohn's disease (five [9%]), anaemia (four [7%]), nasopharyngitis (three [5%]), and fatigue (three [5%]). Eight (15%) participants had serious adverse events, none of which were considered related to the study drug by the investigator. There were no deaths.

Interpretation

This proof-of-concept study showed that tulisokibart is potentially efficacious in moderately to severely active Crohn's disease and is well tolerated. Randomised controlled trials with longer duration are needed to confirm these results; a double-blind, placebo-controlled, phase 3 trial is currently underway.

Funding

Prometheus Biosciences, a subsidiary of Merck & Co, Rahway, NJ, USA.