FDA Approves Preparation Treosulfan With Fludarabine before Allogeneic HSCT for AML, MDS

The injection form of the alkylating agent treosulfan has received a newly approved indication from the FDA. The approval is for use in combination with fludarabine as preparation for allogeneic hematopoietic stem cell transplantation (HSCT) to treat acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS) in adults or pediatric patients aged one year and older. The approval was announced by Medexus Pharmaceuticals Inc. in a press release.

Medexus has developed injection treosulfan as Grafapex, and the agent has Orphan Drug Designation under the Orphan Drug Act. The company holds exclusive commercial rights to this agent in the US via an agreement with medac GmbH, and the approval granted by the FDA is for the sale and use of this agent only in the US. Medexus plans on commercial launch of the agent in the first half of 2025.

“We are pleased to report this positive development, which marks a strategically important step forward for our business and, importantly, will now benefit eligible patients across the United States,” remarked Medexus Chief Executive Officer Ken d’Entremont.

Treosulfan was evaluated in MC-FludT.14/L Trial II, a randomized active-controlled study in which the agent was compared to busulfan plus fludarabine as allogeneic HSCT preparation for adults aged up to 70 years with AML or MDS.

Regarding overall survival (OS) results in the study, measured as time from randomization until death from any cause, the hazard ratio of treosulfan compared with busulfan was 0.67 in the randomized population, 0.73 in patients with AML, and 0.64 in patients with MDS. Adverse reactions that affected 20% or more of patients were edema, infection, musculoskeletal pain, nausea, pyrexia, stomatitis, and vomiting. Laboratory anomaly findings included grade 3 or 4 increases in alanine aminotransferase, aspartate aminotransferase, bilirubin, creatinine, and γ-glutamyl transferase.

The dosing recommended for treosulfan is 10 g/m² daily on days -4, -3, and -2 in combination with fludarabine 30 mg/m² daily on days -6, -5, -4, -3, and -2, and allogeneic HSCT infusion on day 0.

Reference

Medexus announces FDA approval of GRAFAPEX (treosulfan) for injection and provides business update. Press Release. Medexus Pharmaceuticals, Inc. (MDP). January 22, 2025. Accessed January 24, 2025.