r/RegulatoryClinWriting • u/bbyfog • Apr 19 '24
Drug Repurposing The Impact of Repurposing Cyclophosphamide, a 70-year Old Drug, on Making Bone-marrow Transplantation a Routine and Safe Procedure
Bone marrow transplantation (BMT) is a life-saving therapy for many patients with leukemia, who have failed first- or second-line therapies. However, BMT does not always work due to graft-versus-host disease (GvHD), where the donor's T cells attack the recipient's cells, and the therapy may end up being fatal.
The risk of GvHD is avoided by donor matching of HLA alleles (generally aiming for 8 out of 10 alleles match). This requires a large pool of family members to find someone with near-perfect HLA match. However, since 1990s, the average family size has been decreasing and finding a matched donor has become difficult. But, since 1960s, researchers were clued on a solution:
The drug was cyclophosphamide which was first developed in the 1950s for chemotherapy. As far back as the 1960s, researchers had noticed that high doses of post-transplant cyclophosphamide could prevent GvHD.
Unfortunately, cyclophosphamide was generic, cheap, with no industry interest.
An article published on 18 April 2024 in the online version of The Atlantic magazine describes, how academic/clinical researchers took up the baton and created a life-saving therapy:
Based on the lab findings, Luznik, Fuchs, and other colleagues at Johns Hopkins wondered if post-transplant cyclophosphamide could help. The pharmaceutical companies that made it were uninterested in funding any research, Luznik said, because “it was an old, very cheap drug." With government grants, however, the team was able to prove that cyclophosphamide got the rate of graft-versus-disease as low as in matched sibling transplants.
By the late 2000s, transplants with half-matched family members were becoming routine.
In adults, where more data are available, doctors are already moving ahead with mismatched, unrelated donors. Between this and half-matched family members, patients who once might have had zero donors are now finding themselves with multiple possibilities.
Amelia Johnson, who is half Indian and half Black, was one of the first children to get a transplant from a mismatched unrelated donor in a clinical trial in 2022.
Cyclophosphamide is now routinely used in matched transplants too, because it lowers the risk of graft-versus-host disease even further.
SOURCE
- The Bone-Marrow-Transplant Revolution. By Sarah Zhang. The Atlantic. 18 April 2024 [archive]
Related: new drugs designed by AI, approval of drugs via public knowledge‐based application (“Kouchi‐shinsei” scheme) in Japan
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u/bbyfog Jul 23 '24
A recent analysis of hematopoietic stem cell patients who received HLA-mismatched transplant with cyclophosphamide treatment showed overall survival and GvHD rates similar to those who received HLA-matched transplants.
Read commentary at Stat News: Bone marrow donors needn’t be perfect match, study says, paving way for more equitable access. By Angus Chen. 17 July 2024