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Darvadstrocel Fails to Outperform Placebo for Complex Perianal Crohn’s Fistulas in Phase 3 Trial
In a large phase 3 randomized controlled trial, darvadstrocel produced combined remission at week 24 in 48.8% of patients compared with 46.3% receiving placebo — a difference of just 2.4 percentage points that was neither clinically meaningful nor statistically significant (95% CI, −5.8 to 10.6; P = .571). This null result failed to replicate the earlier ADMIRE CD trial’s positive findings, raising questions about the robustness and generalizability of darvadstrocel’s efficacy in this indication.
What Was Studied
ADMIRE CD II investigated whether darvadstrocel — a single injection of 120 × 10⁶ allogeneic expanded adipose-derived stem cells — could achieve combined remission at week 24 in adults with Crohn’s disease and complex perianal fistulas who had not responded adequately to immunosuppressive agents or biologics. The trial was designed to extend and validate the earlier positive findings from the ADMIRE CD trial in an expanded international patient population.
How It Was Studied
ADMIRE CD II was a phase 3, double-blind, randomized, placebo-controlled trial enrolling 568 adults with Crohn’s disease and complex perianal fistulas characterized by no more than two internal openings and no more than three external openings. All participants had demonstrated an inadequate response to prior immunosuppressive or biologic therapy, and were recruited across sites in Europe, Israel, and North America. Patients were randomized 1:1 to receive either a single injection of darvadstrocel or placebo, with follow-up extending to week 24 as the primary assessment point. A total of 249 patients in the darvadstrocel arm and 246 in the placebo arm completed the trial.
What Was Observed
- No significant difference in combined remission: At week 24, combined remission was achieved by 138 of 283 patients (48.8%) in the darvadstrocel group versus 132 of 285 patients (46.3%) in the placebo group. The estimated treatment difference of 2.4% was not statistically significant and the confidence interval crossed zero, indicating no detectable benefit (95% CI, −5.8 to 10.6; P = .571).
- Key secondary endpoints also showed no benefit: Clinical remission at week 24 and time to clinical remission both failed to show a statistically significant advantage for darvadstrocel over placebo (P = .515 and P = .374, respectively), indicating a consistent absence of effect across outcome measures.
- Adverse event profiles were virtually identical between groups: Treatment-emergent adverse events were reported in 73.0% of darvadstrocel recipients (203 of 278) and 73.4% of placebo recipients (201 of 274), confirming no new safety signals and no meaningful difference in tolerability between the two arms.
Why This Matters
Darvadstrocel had previously received regulatory approval in Europe based on the original ADMIRE CD trial, making the failure of this confirmatory trial scientifically significant. The inability to demonstrate superiority over placebo in a larger, geographically expanded population — despite a similar study design — calls into question whether the original trial’s positive result was robust or representative. The finding also highlights the challenges of confirming stem cell therapy efficacy in complex perianal Crohn’s disease across diverse patient populations and clinical settings.
How to Read This Result
Although this was a well-powered, high-quality phase 3 randomized trial, the absence of any identified explanation in the abstract for the divergence between ADMIRE CD and ADMIRE CD II — such as differences in patient selection, background therapies, or remission criteria — leaves the reasons for this null finding uncertain and warrants careful interpretation.
Limitations
The abstract does not explicitly report study limitations.