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Duvakitug 900 mg Achieves Endoscopic Response in 48% of Crohn’s Disease Patients Versus 13% on Placebo
In a phase 2b randomised controlled trial, duvakitug 900 mg produced endoscopic response in 48% of patients with moderately to severely active Crohn’s disease compared with 13% on placebo at week 14, representing a 33-percentage-point advantage (95% credible interval 16 to 50) with a posterior probability of superiority exceeding 0.99. The 450 mg dose also met the prespecified Bayesian threshold for success, though with a smaller and less precise estimated effect.
What Was Studied
The trial evaluated whether duvakitug, a monoclonal antibody targeting TNF-like cytokine 1A (TL1A), could produce meaningful endoscopic improvement in adults with moderately to severely active Crohn’s disease, including patients who had previously failed or could not tolerate advanced therapies. The primary endpoint was endoscopic response, defined as a reduction of at least 50% from baseline in the Simple Endoscopic Score for Crohn’s Disease, assessed at 14 weeks.
How It Was Studied
This multicentre, randomised, placebo-controlled phase 2b trial enrolled 139 adults aged 18 to 75 years with moderately to severely active Crohn’s disease, with one participant in the 900 mg group not receiving study drug, yielding a modified intention-to-treat population of 138. Participants were allocated equally (1:1:1) to receive a subcutaneous loading dose of 2250 mg duvakitug followed by either 450 mg or 900 mg every two weeks, or matching placebo on the same schedule. Notably, 57% of patients had prior exposure to at least one advanced therapy, reflecting a treatment-experienced and clinically challenging population. Efficacy was assessed using Bayesian methodology, with a dose declared successful if the posterior probability that its response rate exceeded placebo reached at least 0.90.
What Was Observed
- Endoscopic response at week 14 was substantially higher with duvakitug 900 mg than with placebo: 48% of patients in the 900 mg group achieved the primary endpoint compared with 13% on placebo. The difference in posterior mean response rates was approximately 33 percentage points (95% credible interval 16 to 50), with a posterior probability of superiority greater than 0.99, comfortably exceeding the prespecified threshold.
- The 450 mg dose also met the Bayesian success criterion, though with a narrower and less certain effect: 26% of patients in the 450 mg group achieved endoscopic response versus 13% on placebo, corresponding to a posterior mean difference of 13 percentage points (95% credible interval −3 to 29) and a posterior probability of superiority of 0.94. The credible interval crossing zero indicates residual uncertainty about the true magnitude of benefit at this dose.
- Overall adverse event rates did not reveal a clear dose-dependent safety signal: adverse events were reported in 67% of patients in the 450 mg group, 43% in the 900 mg group, and 48% in the placebo group. The most commonly reported events were nasopharyngitis and headache, both of which occurred at low absolute frequencies across all arms.
- Serious adverse events were infrequent and not concentrated in the higher-dose arm: they occurred in 13% of the 450 mg group, 2% of the 900 mg group, and 11% of the placebo group, suggesting no dose-related escalation in serious risk over the 14-week observation period.
Why This Matters
Duvakitug represents a distinct mechanistic approach to Crohn’s disease treatment through TL1A inhibition, and this trial provides the first phase 2b evidence of endoscopic efficacy in this population. The results are particularly notable given that the majority of enrolled patients had already been exposed to at least one advanced therapy, a group for whom treatment options are often limited. The strength of the 900 mg signal supports progression to phase 3 investigation.
How to Read This Result
While the Bayesian results are encouraging, this is a relatively small, short-duration phase 2b trial with a predominantly White study population and a 14-week endpoint, all of which limit the generalisability of the findings and leave longer-term efficacy and safety questions unanswered.
Limitations
The abstract does not explicitly report study limitations.