Darvadstrocel: A Review in Treatment-Refractory Complex Perianal Fistulas in Crohn’s Disease
- Adis Drug Evaluation
- Published:
- Volume 32, pages 627–634, (2018)
Abstract
Darvadstrocel (Alofisel®) consists of a suspension of expanded human allogeneic adipose-derived mesenchymal stem cells (eASCs). It is the first mesenchymal stem cell (MSC) advanced therapy approved in the EU for the treatment of complex perianal fistulas in adult patients with non-active/mildly active luminal Crohn’s disease, when fistulas have shown an inadequate response to ≥ 1 conventional or biologic therapy. In the pivotal phase 3 ADMIRE-CD trial in this difficult-to-treat patient population, after standard-of-care fistula conditioning, add-on therapy with a single dose of darvadstrocel (120 million eASC) administered into the tissue surrounding complex perianal fistulas was significantly more effective than placebo (saline), with the darvadstrocel group having a higher combined remission rate (i.e. clinically-assessed fistula closure plus MRI-assessed absence of abscesses) at 24 weeks in intent-to-treat (ITT primary analysis), modified ITT and per-protocol analyses. Clinical remission was maintained in > 50% of patients at 52 weeks’ follow-up. Given the very limited treatment options available for this difficult-to-treat rare condition, darvadstrocel is a promising, novel, minimally invasive therapy that represents an important advance in the therapeutic options for complex perianal fistulas in adult patients with non-active/mildly active luminal Crohn’s disease when fistulas have shown an inadequate response to ≥ 1 conventional or biologic therapy.
article original link: click here
References
-
Panés J, Rimola J. Perianal fistulizing Crohn’s disease: pathogenesis, diagnosis and therapy. Nat Rev Gastroenterol Hepatol. 2017;14(11):652–64.
-
Schwartz DA, Ghazi LJ, Reguiero M, et al. Guidelines for the multidisciplinary management of Crohn’s perianal fistulas: summary statement. Inflamm Bowel Dis. 2015;21(4):723–30.
-
Gecse KB, Bemelman W, Kamm MA, et al. A global consensus on the classification, diagnosis and multidisciplinary treatment of perianal fistulising Crohn’s disease. Gut. 2014;63(9):1381–92.
-
Garcia-Olmo D, Schwartz DA. Cumulative evidence that mesenchymal stem cells promote healing of perianal fistulas of patients with Crohn’s disease: going from bench to bedside. Gastroenterology. 2015;149(4):853–7.
-
Lightner AL, Faubion WA. Mesenchymal stem cell injections for the treatment of perianal Crohn’s disease: what we have accomplished and what we still need to do. J Crohns Colitis. 2017;11(10):1267–76.
-
Garcia-Bosch O, Ricart E, Panés J. Review article: stem cell therapies for inflammatory bowel disease – efficacy and safety. Aliment Pharmacol Ther. 2010;32:939–52.
-
European Medicines Agency. Orphan Maintenance Assessment Report. Alofisel (expanded human allogeneic mesenchymal adult stem cells extracted from adipose tissue): treatment of anal fistula 2018. http://www.ema.europa.eu/. Accessed 11 Sep 2018.
-
American Gastroenterological Association Clinical Practice Committee. American Gastroenterological Association medical position statement: perianal Crohn’s disease. Gastroenterology. 2003;125:1503–7.
-
Bermejo F, Guerra I, Algaba A, et al. Pharmacological approach to the management of Crohn’s disease patients with perianal disease. Drugs. 2018;78(1):1–18.
-
Molendijk I, Duijvestein M, van der Meulen-de Jong AE, et al. Immunomodulatory effects of mesenchymal stromal cells in Crohn’s diease. J Allergy. 2012. https://doi.org/10.1155/2012/187408.
-
Panés J, Ordás I, Ricat E. Stem cell treatments for Crohn’s disease. Expert Rev Clin Immunol. 2010;24(4):597–605.
-
Nauta AJ, Fibbe WE. Immunomodulatory properties of mesenchymal stromal cells. Blood. 2007;110(10):3499–506.
-
TiGenix S. A. U. Alofisel (Darvadstrocel): summary of product characteristics. 2018. http://www.ema.europa.eu/. Accessed 10 Sep 2018.
-
de la Portilla F, Alba F, García-Olmo D, et al. Expanded allogeneic adipose-derived stem cells (eASCs) for the treatment of complex perianal fistula in Crohn’s disease: results from a multicenter phase I/IIa clinical trial. Int J Colorectal Dis. 2013;28(3):313–23.
-
EMA Committee for Advanced Therapies. Guidelines on quality, non-clinical and clinical aspects of medicinal products containing genetically modified cells (EMA/CHMP/410869/2006). 2012. http://www.ema.europa.eu/. Accessed 18 Sep 2018.
-
EMA Committee for Advanced Therapies. Reflection paper on stem cell-based medicinal products. 2011. http://www.ema.europa.eu/. Accessed 18 Sep 2018.
-
Panés J, Garcia-Olmo D, Van Assche G, et al. Expanded allogeneic adipose-derived mesenchymal stem cells (Cx601) for complex perianal fistulas in Crohn’s disease: a phase 3 randomised, double-blind controlled trial. Lancet. 2016;388(10051):1281–90.
-
Panés J, Salas A. Mechanisms underlying the beneficial effects of stem cell therapies for inflammatory bowel disease. Gut. 2009;58(7):898–900.
-
Data on file, TiGenix S.A.U, 2018.
-
Panés J, García-Olmo D, Van Assche G, et al. Long-term efficacy and safety of stem cell therapy (Cx601) for complex perianal fistulas in patients with Crohn’s disease. Gastroenterology. 2018;154(5):1334.e4–13342.e4.
-
Panés J, García-Olmo D, Parfionovas A, et al. Patient-reported outcomes in pain and discharge correlate with objective assessments of perianal fistula remission in Crohn’s disease (CD) [abstract no. P594]. J Crohn’s Colitis. 2018;12(Suppl. 1):S408–9.
-
García-Olmo D, Panés J, Brayshaw N, et al. Cx601, a novel stem cell therapy for complex perianal fistulas in Crohn’s disease has rapid onset of clinical remission and low relapse rate by week 52 [abstract no. P691]. J Crohn’s Colitis. 2018;12(Suppl 1):S460–1.
-
Adegbola SO, Pisani A, Sahnan K, et al. Medical and surgical management of perianal Crohn’s disease. Ann Gastroenterol. 2018;31(2):129–39.
-
Schwartz DA, Ghazi LJ, Reguiero M. Guidelines for medical treatment of Crohn’s perianal fistulas: critical evaluation of therapeutic trials. Inflamm Bowel Dis. 2015;21(4):737–52.
-
Gionchetti P, Dignass A, Danese S, et al. 3rd European evidence-based consensus on the diagnosis and management of Crohn’s disease 2016. J Crohn’s Colitis. Part 2: surgical management and special situations. 2017;11(2):135–49.
-
Georgiev-Hristov T, Guadalajara H, Herreros MD, et al. A step-by-step surgical protocol for the treatment of perinanal fistula with adipose-derived mesenchymal stem cells. J Gastrointest Surg. 2018. https://doi.org/10.1007/s11605-018-3895-6.
-
Molendijk I, Van der Meulen-de Jong AE, Verspaget HW, et al. Standardization of mesenchymal stromal cell therapy for periananl fistulizing Crohn’s disease. Eur J Gastroenterol Hepatol. 2018;30(10):1148–54.
-
Jani M, Dixon WG, Chinoy H. Drug safety and immunogenicity of tumour necrosis factor inhibitors: the story so far. Rheumatology. 2018. https://doi.org/10.1093/rheumatology/kex434.
-
McConachie SM, Wilhelm SM, Bhargava A, et al. Biologic-induced infections in inflammatory bowel disease: the TNF-α antagonists. Ann Pharmacother. 2018;52(6):571–9.
-
Lightner AL, Wang Z, Zubair AC, et al. A systematic review and meta-analysis of mesenchymal stem cell injections for the treatment of perianal Crohn’s disease: progress made and future directions. Dis Colon Rectum. 2018;61(5):629–40.
-
Ciccocioppo R, Klersy C, Leffler D, et al. Safety and efficacy of local injections of mesenchymal stem cells in perianal fistula in Crohn’s disease: a systematic review and meta-analysis of the clinical trials and observational cohort studies [abstract no. Mo1653]. Gastroenterology. 2018;154(6 Suppl 1):784–5.
A WordPress Commenter
August 26, 2025Hi, this is a comment. To get started with moderating, editing, and deleting comments, please visit the Comments screen in the dashboard. Commenter avatars come from Gravatar.