Darvadstrocel Findings in ADMIRE CD II Phase 3 Trial

Key Takeaways

• A phase 3 double-blind placebo-controlled randomized trial enrolled adults with complex perianal fistulizing Crohn's disease after inadequate response to immunosuppressive agents or biologics and used standardized local procedures.
• Week 24 combined remission was similar with darvadstrocel and placebo, and the primary endpoint was not met.
• Treatment-emergent adverse event rates were similar between groups, and investigators did not identify new safety signals.

In adults with Crohn's disease and complex perianal fistulas, ADMIRE CD II reported week 24 combined remission in 48.8% of patients assigned to darvadstrocel and 46.3% assigned to placebo. The phase 3 trial compared darvadstrocel with placebo in adults who had not responded adequately to immunosuppressive agents or biologics. Although remission numerically favored darvadstrocel, the difference was modest at the primary analysis.

This phase 3, double-blind, randomized, placebo-controlled trial was conducted across sites in Europe, Israel, and North America. Eligible participants were adults with Crohn's disease and complex perianal fistulas, limited to no more than 2 internal openings and no more than 3 external openings. Enrollment also required inadequate response to immunosuppressive agents or biologics, keeping the study centered on patients with prior treatment failure. Overall, 568 patients were randomized 1:1, with 283 assigned to darvadstrocel and 285 assigned to placebo.

Darvadstrocel was given 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, combined remission at week 24, was defined as closure of all treated external openings together with absence of collections larger than 2 cm. The estimated treatment difference for that endpoint was 2.4%, with a 95% confidence interval from -5.8 to 10.6 and P = .571. Key secondary endpoints also were not significantly different, including clinical remission at week 24, with P = .515, and time to clinical remission, with P = .374. Efficacy findings were similar between groups at the prespecified primary time point.

Completion counts were 249 in the darvadstrocel group and 246 in the placebo group. Treatment-emergent adverse events occurred in 203 of 278 patients, or 73.0%, with darvadstrocel and 201 of 274, or 73.4%, with placebo. Event rates were similar between the 2 study arms. Investigators did not identify new safety signals for darvadstrocel. ADMIRE CD II did not meet its primary endpoint of combined remission at week 24 at the prespecified assessment.