Biology:Darvadstrocel
Darvadstrocel, sold under the brand name Alofisel, is 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 contains 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Union in March 2018.[2] The approval was spearheaded by data published in the ADMIRE-CD trial.[2][3] Darvadstrocel was withdrawn from the EU market in December 2024.[4]
It was approved for use in Japan by Japan's Ministry of Health, Labour and Welfare (MHLW) in September 2021.[5] In January 2026, the marketing of Alofisel in Japan was discontinued.[6]
Medical use
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]
Mechanism of action
Darvadstrocel works by reducing inflammation and facilitating the growth of tissue in the fistula tract.[2][3]
History
ADMIRE-CD
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][7] 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]
INSPECT
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.[8] The study data showed that darvadstrocel or the maintenance treatment used can have long term clinical remission in patients.[8]
ADMIRE-CD II
ADMIRE-CD II was an international, randomized double-blind placebo-controlled trial of the efficacy and safety of Alofisel (darvadstrocel) in treating complex perianal fistulas in 568 patients with Crohn's disease in whom immunosuppressive agents or biologics had failed.[9] The primary outcome (rate of combined remission at 24 weeks) was similar between treatments (48.8% darvadstrocel vs 46.3% placebo), as were all secondary outcomes. In December 2024, the European Medicines Agency withdrew the marketing authorization for Alofisel (darvadstrocel) upon request of Takeda Pharma.[10]
Society and culture
Legal status
In 2023, darvadstrocel was approved for medical use in Israel, Switzerland, Serbia, the United Kingdom, and Japan.[11] Darvadstrocel was withdrawn from the European Union market in December 2024.[4] In January 2026, Takeda Pharma discontinued sales of Alofisel in Japan.[6]
References
- ↑ Cite error: Invalid
<ref>tag; no text was provided for refs namedAlofisel SmPC - ↑ 2.0 2.1 2.2 2.3 2.4 "Alofisel EPAR". 4 April 2018. https://www.ema.europa.eu/en/medicines/human/EPAR/alofisel.
- ↑ 3.0 3.1 3.2 3.3 3.4 3.5 3.6 3.7 "Long-term Efficacy and Safety of Stem Cell Therapy (Cx601) for Complex Perianal Fistulas in Patients With Crohn's Disease". Gastroenterology 154 (5): 1334–1342.e4. April 2018. doi:10.1053/j.gastro.2017.12.020. PMID 29277560.
- ↑ 4.0 4.1 "Alofisel withdrawn from the EU market". European Medicines Agency (EMA) (Press release). 13 December 2024. Retrieved 16 December 2024.
- ↑ NS Healthcare Staff Writer (28 September 2021). "Takeda's Alofisel approved in Japan to treat fistulas in patients with Crohn's disease". NS Healthcare. https://www.ns-healthcare.com/news/takedas-alofisel-approved-in-japan/.
- ↑ 6.0 6.1 "Takeda to Halt Sales of Cell Therapy Alofisel in Japan". https://pj.jiho.jp/article/254573.
- ↑ "Adipose Derived Mesenchymal Stem Cells for Induction of Remission in Perianal Fistulizing Crohn's Disease (ADMIRE-CD)". https://www.clinicaltrials.gov/ct2/show/NCT01541579.
- ↑ 8.0 8.1 "INSPECT: A Retrospective Study to Evaluate Long-term Effectiveness and Safety of Darvadstrocel in Patients With Perianal Fistulizing Crohn's Disease Treated in the ADMIRE-CD Trial". Inflammatory Bowel Diseases 28 (11): 1737–1745. November 2022. doi:10.1093/ibd/izab361. PMID 35099555.
- ↑ "OP18 Efficacy and safety of darvadstrocel treatment in patients with complex perianal fistulas and Crohn's Disease: results from the global ADMIRE-CD II phase 3 study" (in en). Journal of Crohn's and Colitis 18 (Supplement_1): i34–i35. 24 January 2024. doi:10.1093/ecco-jcc/jjad212.0018. ISSN 1873-9946.
- ↑ "Alofisel". https://www.ema.europa.eu/en/medicines/human/EPAR/alofisel.
- ↑ "Takeda announces topline results of phase 3 ADMIRE-CD II trial of Alofisel". Takeda Pharmaceuticals (Press release). Retrieved 15 December 2024.
Further reading
- "Darvadstrocel for the treatment of patients with perianal fistulas in Crohn's disease". Drugs of Today 55 (2): 95–105. February 2019. doi:10.1358/dot.2019.55.2.2914336. PMID 30816884.
- "Darvadstrocel for the treatment of perianal fistulas in Crohn's disease". Expert Review of Gastroenterology & Hepatology 14 (6): 405–410. June 2020. doi:10.1080/17474124.2020.1764349. PMID 32354239.
- "Evaluation of Advanced Therapy Medicinal Products by the National Institute for Health and Care Excellence (NICE): An Updated Review". PharmacoEconomics - Open 6 (2): 147–167. March 2022. doi:10.1007/s41669-021-00295-2. PMID 34415514.
- "Darvadstrocel: A Review in Treatment-Refractory Complex Perianal Fistulas in Crohn's Disease". BioDrugs 32 (6): 627–634. December 2018. doi:10.1007/s40259-018-0311-4. PMID 30298387.
External links
- "Darvadstrocel for treating complex perianal fistulas in Crohn's disease". NICE. 9 January 2019. https://www.nice.org.uk/guidance/TA556.
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