FDA approves Grafapex combo for bone marrow transplant with AML
Given with fludarabine as conditioning prior to transplant for blood cancer
The U.S. Food and Drug Administration (FDA) has approved Grafapex (treosulfan), an injectable chemotherapy, as part of the drug regimen for adults and children with acute myeloid leukemia (AML) or myelodysplastic syndrome waiting to receive a stem cell transplant from a healthy donor.
The FDA’s decision was supported by data from a Phase 3 clinical trial (NCT00822393), which found the drug was effective when used in combination with fludarabine in preparing for a bone marrow transplant. The approval covers patients, 1 year old and older, with either blood cancer.
Medexus Pharmaceuticals, the therapy’s developer, expects Grafapex to be available in the U.S. by midyear.
“This FDA approval provides a useful option for adult and pediatric patients, with the potential to enhance overall survival while minimizing side effects,” Filippo Milano, MD, PhD, a stem cell transplant specialist at the Fred Hutchinson Cancer Center in Washington and a principal investigator in clinical trials of the treatment, said in a company press release.
Chemotherapy given as conditioning prior to bone marrow transplant
Acute leukemia occurs when genetically mutated hematopoietic stem cells — the bone marrow cell that gives rise to all types of blood cells — begin to grow out of control and disperse throughout the bloodstream.
In AML, the most common type of acute leukemia in adults, the disease specifically affects the myeloid stem cells that can become red blood cells, platelets, and granulocytes, a type of white blood cell.
Stem cell transplant, also known as a bone marrow transplant, is one way of treating AML. This procedure is designed to replace diseased hematopoietic stem cells and restore the body’s ability to produce healthy blood cells. When transplanted stem cells come from a healthy donor, the process is an allogeneic transplant.
However, patients must first undergo conditioning to prepare for transplantation, for reasons including making room for the transplanted stem cells and suppressing the immune system to help prevent rejection. Conditioning typically involves high doses of chemotherapy.
Grafapex is a type of chemotherapy known as an alkylating agent, which breaks DNA strands. These breaks prevent the DNA from being copied, stopping the cell from dividing. Cancer cells, which divide rapidly, are particularly susceptible to DNA damage, and Grafapex aims to effectively kill these cells prior to the transplant.
As part of the conditioning treatment, Grafapex is designed to be used alongside fludarabine, another chemotherapy affecting cancer cell growth.
Grafapex combo showed efficacy in AML patients awaiting transplant
The Phase 3 clinical trial assessed the efficacy and safety of conditioning with fludarabine and Grafapex prior to a bone marrow transplant in 570 adults with AML or myelodysplastic syndrome at sites across Europe. Patients were randomized to either a combination of fludarabine and Grafapex or fludarabine and busulfan, a chemotherapy widely used in conditioning regimens.
Trial findings, published in 2020 in The Lancet Haematology journal, found the fludarabine and Grafapex combination equally effective as fludarabine and busulfan.
In AML patients, the risk of death was 27% lower with the Grafapex combo compared with that using busulfan, although this reduction was not statistically significant. At two years after the transplant, 64% of patients in the Grafapex group and 50.4% in the busulfan group were alive and free of disease progression or complications.
Common treatment side effects included nausea, infections, and vomiting.
The FDA previously designated Grafapex an orphan drug, a status that provides incentives for potential treatments for rare diseases. This designation includes about seven years of market exclusivity, a period during which the FDA cannot approve a competing product for the same indication.
“Not only will Grafapex make a substantial contribution to [allogeneic stem cell transplants] in the United States, but it also solidifies Medexus’s leadership position in this therapeutic field,” said Ken d’Entremont, Medexus CEO. “We are pleased to report this positive development, which … will now benefit eligible patients across the United States.”
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