Darvadstrocel falls short for Crohn’s in phase 3 trial

A large international phase 3 trial found that darvadstrocel — an allogeneic adipose-derived stem cell therapy — did not significantly improve remission rates compared with placebo in patients with Crohn’s disease and complex perianal fistulas, according to results published in Gastroenterology.

 

Perianal fistulas are a common complication of Crohn’s disease, with approximately 70%–80% classified as complex when they involve deeper sphincter structures or multiple tracts. These fistulas can cause severe pain, infection, and diminished quality of life, and they often persist despite treatment with biologics, immunosuppressants, or surgery, noted Jean-Frédéric Colombel, MD, of The Dr. Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, and colleagues.

 

The multi-institutional group of investigators conducted the ADMIRE CD II trial, a phase 3, randomized, double-blind, placebo-controlled study. The trial enrolled 568 adults with Crohn’s disease and complex perianal fistulas across sites in Europe, Israel, and North America. All participants had failed prior therapy with immunosuppressants or biologics, and were randomized 1:1 to receive a single local injection of darvadstrocel — containing 120 million expanded adipose-derived mesenchymal stem cells — or placebo following standard surgical preparation of the fistula tract, including curettage and closure of the internal opening.

 

The primary endpoint was combined remission at week 24, defined as closure of all treated external openings together with absence of fluid collections larger than 2 cm on imaging. Of the 568 randomized patients, 249 in the darvadstrocel group and 246 in the placebo group completed the study.

 

At 24 weeks, combined remission occurred in 48.8% of patients receiving darvadstrocel compared with 46.3% of those receiving placebo, a difference that was not statistically significant. Secondary outcomes — including clinical remission rates and time to remission — also showed no meaningful differences between the two treatment groups.

 

Safety outcomes were similar between the groups, noted investigators. Treatment-emergent adverse events occurred in roughly 73% of patients in both arms, and there were no new safety signals associated with the stem cell therapy.

 

In terms of limitations, the authors noted that the reason why ADMIRE CD II did not meet its primary endpoint of combined remission at week 24 cannot be definitely determined by this study alone.

 

Darvadstrocel had previously shown promising results in earlier studies. However, the ADMIRE CD II findings suggest that its benefit may not extend consistently to broader or more heterogeneous patient populations. 

 

While not definitive, several factors may help explain these neutral results. The study included patients with highly complex fistulas and prior treatment failures, potentially representing a particularly refractory group. In addition, both arms received surgical preparation and optimized standard care, which may have improved outcomes in the placebo group and reduced the ability to detect a treatment effect, noted investigators.

 

Future research may focus on identifying patient subgroups more likely to benefit from cellular therapy, refining delivery techniques, or combining regenerative approaches with biologic or immunomodulatory treatments. The authors also note that, because prior meta-analyses have suggested darvadstrocel could indeed be effective for perianal fistula healing, further research is needed that focuses on other cell types, such as regulatory T cells, or else on other stem cell components and pathways.  For now, however, darvadstrocel’s role in routine management of complex Crohn’s perianal fistulas remains uncertain.

 

"The results of this study impact the availability of darvadstrocel for patients with perianal fistulizing Crohn’s disease and challenge the relevance of stem cell therapy for perianal fistula healing. However, meta-analyses have suggested that stem cell therapy is effective in this context. Therefore, newer research focusing on stem cell pathways and components (such as extracellular vesicles) or other cell types (such as regulatory T cells) continue," concluded investigators.