Home > Gastroenterology > DDW 2024 > Inflammatory Bowel Disease Therapies > ADMIRE-CD II: Darvadstrocel does not meet primary endpoint in complex Crohn’s perianal fistulas

ADMIRE-CD II: Darvadstrocel does not meet primary endpoint in complex Crohn’s perianal fistulas

Presented by
Dr Laura Raffals, Mayo Clinic, USA
Conference
DDW 2024
Trial
Phase 3, ADMIRE-CD II
Doi
https://doi.org/10.55788/646add85
The phase 3 ADMIRE-CD II study evaluated the efficacy and safety of darvadstrocel, an allogeneic mesenchymal stem cell therapy, for complex perianal fistulas in Crohn’s disease. Despite rigorous fistula preconditioning, darvadstrocel did not significantly outperform placebo at 24 weeks.

The findings of the global, randomised, double-blind, placebo-controlled ADMIRE-CD II trial (NCT03279081) were shared by Dr Laura Raffals (Mayo Clinic, MN, USA) [1]. A total of 568 participants were randomised 1:1 to receive either a single dose of darvadstrocel or a placebo. Preconditioning involved curettage, seton placement, and closure of internal openings before administering the treatment. The primary endpoint was combined remission at 24 weeks, defined as the closure of all treated external openings that were draining at baseline. Secondary endpoints included combined remission at 52 weeks, clinical remission at 24 and 52 weeks, and the time to clinical remission at 24 weeks.

At 24 weeks, combined remission was achieved by 48.8% in the darvadstrocel group and 46.3% in the placebo group, with a non-significant difference (Δ2.4%; 95% CI -5.8 to 10.6; P=0.571). Combined remission rates at 52 weeks remained non-significant between darvadstrocel and placebo groups (39.7% vs 41%; Δ1.3%; 95% CI -6.8 to 9.3; P=0.757). The authors, however, emphasised that the placebo response rate was unexpectedly high, particularly after the onset of the COVID-19 pandemic.

The safety profile showed that darvadstrocel was well tolerated, with safety patterns comparable with placebo.

“Treatment of complex perianal fistulas with a single dose of darvadstrocel showed no statistically significant or clinically meaningful differences in our key efficacy endpoints when compared with placebo, noting that the placebo group also received fistula preconditioning. An unexpectedly high response rate was observed in the placebo group,” Dr Raffals concluded.


    1. Raffals L, et al. Efficacy and safety of darvadstrocel treatment in patients with complex perianal fistulas and Crohn’s disease: results from the global ADMIRE-CD II phase 3 study. 761, DDW 2024, 18–21 May, Washington DC, USA.

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