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Chronic Graft-Versus-Host Disease

There remains a significant unmet medical need in chronic graft-versus-host disease (GVHD).

Chronic GVHD, an immune response of the donor-derived hematopoietic cells against recipient tissues, is a serious, potentially life-threatening complication of allogeneic hematopoietic stem cell transplantation, or HSCT, that can last for years. This can lead to significant health related impairments and tremendous disease burden, even in patients cured from their underlying hematologic disorder.1

Chronic GVHD is the most common long-term complication of the allogeneic hematopoietic stem cell transplant, affecting up to 50% of all transplant recipients.2-4 It is estimated that approximately 14,000 U.S. patients suffer from chronic GVHD, 50% of whom require treatment beyond second line due to disease progression, inadequate response, or disease manifestations that aren’t fully addressed with current treatments.5,6 Chronic GVHD pathophysiology is driven by chronic inflammation and fibrosis that may lead to end-organ damage7 and the disease typically manifests across multiple organ systems, with skin and mucosa being commonly involved.8

Corticosteroids are the cornerstone of therapy; however, approximately 60% of patients develop corticosteroid resistance or dependence during their course of treatment. Other approved therapies after steroids are generally not curative, and patients often cycle through many therapies.17

 

References:

  1. Yu et al. Cancer Med. 2023;12:3623-3633.
  2. Arai et al. Biol Blood Marrow Transplant. 2015;21:266-274.
  3. Arora et al. Biol Blood Marrow Transplant. 2016;22:449-455.
  4. Velickovic et al. Ther Adv Hematol. 2020;11:1-18.
  5. A phase 1 study to evaluate SNDX-6352 in subjects with active cGVHD. ClinicalTrials.govidentifier: NCT03604692. https://clinicaltrials.gov/ct2/show/NCT03604692. Updated August 6, 2019. Accessed May 6, 2020.
  6. Data on file. Syndax Pharmaceuticals, Inc.
  7. (Cooke 2017; 3A,4A,44A | Buxbaum 2023; 6A)
  8. Alexander K et al. CSF-1-dependant donor-derived macrophages mediate chronic graft-versus-host disease. Journal of Clinical Investigation. October 2014. 10.1172/JC195935. 4367-4280.
  9. Jagasia MH, et al. Biol Blood Marrow Transplant. 2015;21(3):389-401.
  10. Vigorito AC, et al. Blood. 2009;114(3):702-708.
  11. Lee SJ, et al. Blood. 2002;100(2):406-414.
  12. Vukic T, et al. Croat Med J. 2016;57(3):266-275.
  13. Inamoto Y, et al. Arthritis Rheumatol. 2014;66(4):1044-1052.
  14. Hamilton BK, et al. Bone Marrow Transplant. 2017;52(6):803-810.
  15. Blazar BR, et al. Nat Rev Immunol. 2012;12(6):443-458.
  16. Cooke KR, et al. Biol Blood Marrow Transplant. 2017;23(2):211-234.
  17. Lee et al. Biol Blood Marrow Transplant. 2018;24:555-562.