Clinical data | |
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Trade names | Alofisel |
Other names | CX-601 |
Routes of administration | Injection |
ATC code | |
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KEGG |
Darvadstrocel, sold under the brand name Alofisel, was a medication used to treat complex perianal fistulas in adults with non-active/mildly active luminal Crohn's disease when fistulas have shown an inadequate response to at least one conventional or biologic therapy. [1] It contained mesenchymal stem cells from fat tissue of adult donors. [2]
It was approved for use in the European Union in March 2018. [2] The approval was spearheaded by data published in the ADMIRE-CD trial [2] [3] and withdrawn from the EU market in 2024 [4] .
It was approved for use in Japan by Japan's Ministry of Health, Labour and Welfare (MHLW) in September 2021. [5]
Darvadstrocel was approved by the European Union for the treatment of adults with complex Crohn's perianal fistulas after conventional or biological medications have not worked [2] until it was withdrawn.
Darvadstrocel was thought to work by reducing inflammation and facilitating the growth of tissue in the fistula tract. [2] [3]
The ADMIRE-CD trial was a phase III trial that assessed the safety and efficacy of darvadstrocel vs. placebo in adults with complex perianal fistulas with Crohn's disease. [3] [6] The study randomized a total of 212 patients. [3] 107 patients were given darvadstrocel and 105 patients were given placebo. [3]
After one year, the study found darvadstrocel to be effective in closing external fistula openings, compared to placebo. [3] Patients taking darvadstrocel had a combined remission of 56.3% and clinical remission of 59.2%. [3] The placebo controls had a combined remission of 38.6% and clinical remission of 41.6%. [3]
Published in 2022, the INSPECT study is a retrospective study that evaluated the long-term effectiveness and safety of darvadstrocel in patients with perianal fistulas in Crohn's disease that were treated in the ADMIRE-CD trial. [7] The study data showed that darvadstrocel or the maintenance treatment used can have long term clinical remission in patients. [7]
The Phase 3 ADMIRE-CD II study, assessing the efficacy and safety of Alofisel® (darvadstrocel) for the treatment of complex Crohn’s Perianal Fistulas (CPF), did not meet its primary endpoint of combined remission at 24 weeks, based on topline data. The safety profile for darvadstrocel was consistent with prior studies and there were no new safety signals identified [8] .
Crohn's disease is a chronic inflammatory bowel disease characterized by recurrent episodes of intestinal inflammation, primarily manifesting as diarrhea and abdominal pain. Unlike ulcerative colitis, inflammation can occur anywhere in the gastrointestinal tract, though it most frequently affects the ileum and colon, involving all layers of the intestinal wall. Symptoms may be non-specific and progress gradually, often delaying diagnosis. About one-third of patients have colonic disease, another third have ileocolic disease, and the remaining third have isolated ileal disease. Systemic symptoms such as chronic fatigue, weight loss, and low-grade fevers are common. Organs such as the skin and joints can also be affected. Complications can include bowel obstructions, fistulas, nutrition problems, and an increased risk of intestinal cancers.
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Management of Crohn's disease involves first treating the acute symptoms of the disease, then maintaining remission. Since Crohn's disease is an immune system condition, it cannot be cured by medication or surgery. Treatment initially involves the use of medications to eliminate infections and reduce inflammation. Surgery may be required for complications such as obstructions, fistulae, abscesses, or if the disease does not respond to drugs within a reasonable time. However, surgery cannot cure Crohn's disease. It involves removing the diseased part of the intestine and rejoining the healthy ends, but the disease tends to recur after surgery.
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TiGenix is a European cell therapy company with a proprietary validated allogeneic expanded adipose-derived stem cell (eASC) platform technology for the treatment of autoimmune and inflammatory diseases, and a commercialized product. Its corporate headquarters are in Leuven, Belgium, and it has operations in Madrid, Spain. TiGenix was founded in 2000 by Prof. Dr. Frank P. Luyten and Gil Beyen as a spin-off from the Katholieke Universiteit Leuven and the Ghent University.
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Risankizumab, sold under the brand name Skyrizi, is a humanized monoclonal antibody used for the treatment of plaque psoriasis, psoriatic arthritis, Crohn's disease, and ulcerative colitis. It is designed to target interleukin 23A (IL-23A). It is given by subcutaneous injection.
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