Stem Cell Therapy for Perianal Fistulas in Crohn's Disease

What This Article Covers

Complex perianal fistulas—abnormal tunnels that form between the bowel and the skin near the anus—are among the hardest complications of Crohn's disease to treat, often resisting antibiotics, biologics, and repeated surgery. A locally injected, donor-derived mesenchymal stem cell product called darvadstrocel (brand name Alofisel) became the first cell therapy approved anywhere specifically for this problem, backed by a genuinely positive pivotal trial. But its story since then is a case study in why regulators require confirmatory trials: a larger follow-up study failed to reproduce the original benefit, and the manufacturer voluntarily withdrew the product from the European market in late 2024. This article covers what the evidence actually showed, what changed, and where things stand now for patients and the field.

How It's Thought to Work

Darvadstrocel is made of allogeneic (donor-derived) mesenchymal stem cells expanded from adult adipose (fat) tissue, injected directly into and around the walls of the fistula tract during a single outpatient procedure, typically after the tract has been surgically prepared. Rather than acting systemically, the cells are thought to work locally—calming the inflammatory signaling that keeps a fistula tract open and creating conditions more favorable for the tissue to close—without the broad immunosuppression that comes with drugs like anti-TNF biologics. That targeted, one-time-injection approach, aimed at the fistula itself rather than the whole immune system, is part of what made the therapy so appealing when it first emerged.

What the Evidence Shows

The case for darvadstrocel rested heavily on the original ADMIRE-CD trial, which randomized 212 patients with treatment-refractory complex perianal fistulas. At 24 weeks, 51.5% of darvadstrocel recipients achieved combined remission versus 35.6% on placebo, a benefit that held up through 52 weeks (56.3% vs. 38.6%), with a safety profile that looked reassuring at the time (Takeda, 2023). That result was strong enough to win Alofisel approval from the European Medicines Agency in March 2018—the first stem cell therapy approved in Europe for Crohn's-related fistulas—with Japan approving it a few years later.

Regulators required a larger confirmatory trial, ADMIRE-CD II, enrolling 568 patients at sites including the United States. When Takeda reported results, the news was sobering: the trial did not meet its primary endpoint of combined remission at 24 weeks, with 48.8% of darvadstrocel patients versus 46.3% of placebo patients achieving remission—no meaningful difference—and no significant separation on secondary endpoints either (Takeda, 2023; GI & Hepatology News, 2026). Safety stayed consistent with the earlier studies, with no new safety signals, so this was a failure of effectiveness, not harm. The full peer-reviewed results, published in Gastroenterology, suggest that unusually well-optimized surgical and medical background care in both trial arms, combined with an especially treatment-resistant patient population, may have narrowed the gap the first trial had detected. Following this outcome, Takeda voluntarily withdrew Alofisel's EU marketing authorization, a decision the European Commission finalized on December 13, 2024 (EMA, 2024). Darvadstrocel has never been approved by the FDA, and no U.S. approval is currently anticipated.

Who Might Be a Candidate

Because Alofisel is no longer commercially available in the EU and was never approved in the United States, there is currently no approved stem cell product that clinicians can prescribe for this indication. Historically, when the therapy was available, candidacy was defined narrowly:

• Adults with Crohn's disease and complex perianal fistulas (tracts involving significant sphincter muscle, multiple openings, or rectovaginal extension)
• Non-active or only mildly active luminal (bowel) Crohn's disease at the time of treatment
• Inadequate response to at least one conventional or biologic therapy
• Fistula tracts surgically prepared beforehand (draining setons removed, abscesses drained)
• No active perianal sepsis or untreated abscess
• Willingness to undergo a single outpatient injection rather than ongoing systemic drug therapy

Patients interested in cell-based approaches today are best served asking their gastroenterologist or colorectal surgeon about active trials of newer candidates—different cell sources, regulatory T cells, or cell-derived extracellular vesicles—rather than seeking Alofisel itself.

Bottom Line

Darvadstrocel's arc is a rare, well-documented example of a promising stem cell therapy that looked genuinely effective in one well-run trial and then did not hold up in a larger, more rigorous one—not because it was unsafe, but because its benefit no longer stood out against increasingly good standard care. It remains a meaningful proof of concept that local cell injection can be feasible and safe for an especially hard-to-treat complication, and its evidence base is unusually transparent about both the early success and the later disappointment. For now, though, it isn't an option patients can obtain: it's withdrawn in Europe, was never approved in the U.S., and its future depends on whether researchers can identify a responsive patient subgroup or a next-generation cell therapy that reproduces the original signal.