Darvadstrocel Misses Primary Endpoint in ADMIRE CD II Trial

Key Takeaways

• Week-24 combined remission was similar between darvadstrocel and placebo, and the primary endpoint was not met.
• Key secondary efficacy measures, including clinical remission at week 24 and time to clinical remission, were also similar between groups.
• Treatment-emergent adverse events occurred at similar rates in both groups, and no new safety signals were identified.

In ADMIRE CD II, week-24 combined remission was 48.8% with darvadstrocel and 46.3% with placebo in a randomized, placebo-controlled phase 3 trial in adults with complex perianal fistulizing Crohn’s disease. This was the trial’s main efficacy comparison after local surgical preparation in both groups. The primary endpoint was not met.

ADMIRE CD II was a phase 3, double-blind, randomized, placebo-controlled trial conducted in Europe, Israel, and North America. Participants were adults with Crohn’s disease and complex perianal fistulas, with no more than 2 internal openings and no more than 3 external openings, and had an inadequate response to immunosuppressive agents or biologics.

A total of 568 patients were randomized 1:1, with 283 assigned to darvadstrocel and 285 to placebo; 249 and 246 patients, respectively, completed the trial. Darvadstrocel was administered as a dispersion of 120 × 10^6 stem cells in 24 mL sterile buffered solution, and both groups underwent curettage and closure of the internal opening. The primary endpoint was combined remission at week 24, defined as closure of all treated external openings with no collections larger than 2 cm.

At week 24, 138 of 283 patients in the darvadstrocel group and 132 of 285 in the placebo group achieved combined remission. The estimated treatment difference was 2.4% (95% CI, -5.8 to 10.6; P = .571). Key secondary endpoints also did not differ significantly, including clinical remission at week 24 (P = .515) and time to clinical remission (P = .374). Across the reported efficacy measures, no statistically significant differences were observed between groups.

Treatment-emergent adverse events occurred in 203 of 278 patients, or 73.0%, in the darvadstrocel group and 201 of 274, or 73.4%, in the placebo group. No new safety signals were identified during the trial.

ADMIRE CD II did not meet its primary endpoint, and the safety findings did not identify new concerns.