Background and Aims Previous studies conducted in Europe suggested that darvadstrocel, a suspension of expanded allogeneic adipose-derived mesenchymal stem cells, is safe and effective for treatment-refractory complex perianal fistulas in patients with Crohn’s disease. The aim of this study was to evaluate the efficacy and safety of darvadstrocel for the treatment of complex perianal fistulas in Japanese adults with Crohn’s disease. Methods This is a phase 3, open-label, single-arm study conducted at 9 sites in Japan. Adult patients with non-active or mildly active Crohn’s disease and complex perianal fistulas received a single 24mL intralesional injection of darvadstrocel (120×10 6 cells). The primary endpoint was combined remission (clinically confirmed closure of all treated external openings that were draining at screening and absence of collections >2 cm [confirmed by magnetic resonance imaging] among treated fistulas) at Week 24. Results Between March 6, 2019 and February 1, 2021, 22 patients received darvadstrocel and completed the 52-week follow-up. The proportion of patients achieving combined remission at Week 24 was 59.1% (95% CI, 38.5–79.6). The effect was maintained at Week 52, with 68.2% (95% CI, 48.7–87.6) of patients achieving combined remission. Treatment-related adverse events included: 1 (4.5%) patient with worsening of Crohn’s disease and diarrhea and 1 (4.5%) patient with blood bilirubin increase. No new safety findings were identified in this study. Conclusions The efficacy and tolerability of darvadstrocel in Japanese adult patients with treatment-refractory complex perianal fistulas in Crohn’s disease were similar to those observed in the previous European study.

Background Patients with complex Crohn’s perianal fistulas were treated with allogenic mesenchymal stem cells (darvadstrocel) in pivotal studies, and in clinical practice in Europe since, 2018. However, it is unclear whether the same efficacy and safety could be expected across different ethnic groups. Moreover, it is known that perianal complications including perianal fistulas are more frequent in Asian patients with Crohn’s disease (CD). Methods Japanese adult patients with treatment-refractory complex perianal fistulas in CD were enrolled from, 9 sites in a phase, 3, open-label, single-arm, uncontrolled study. Patients could have, 2 internal and, 3 external openings at maximum, and their luminal disease was non-active or mildly active (CDAI ≤220) at baseline. A single dose (24mL, 120 million cells) of darvadstrocel was intralesionally injected, and results after, 24 and, 52 weeks were evaluated. Primary endpoint was combined remission (a remission rate evaluated clinically and by MRI) at Week 24. Results 22 patients (mean age, 36.4 years, 63.6% male, mean duration of CD, 11.3 years) were enrolled. A half (11/22) had, 1 internal opening (IO) and, 2 external openings (EO) followed by, 1IO-1EO/2IO-2EO/2IO-3EO (3 each, 9/22) and, 1IO-3EO (2/22)., 59.1% and, 68.2% achieved combined remission at Week, 24 (primary endpoint) and Week, 52, respectively. Up to Week, 52, 90.9% (20/22) experienced adverse events (AE), and, 81.8% (18/22) were mild or moderate in intensity. Proctalgia (6/22), nasopharyngitis (5/22), and anal fistula (4/22) were most frequently reported. There was no death or AE-related study discontinuation. Conclusion 52 weeks after administrating darvadstrocel in Japanese patients with complex perianal fistulas in CD, fistula closure was confirmed in, 68% (15/22) and partial closure in, 90.0% (20/22). These findings are consistent with the pivotal study ADMIRE-CD, and real-world case-series reported from Europe. Furthermore, no new safety concerns were identified.