The U.S. Food and Drug Administration (FDA) has granted approval to GRAFAPEX (treosulfan) for injection, an alkylating agent, to be used in combination with fludarabine as a preparative regimen for allogeneic hematopoietic stem cell transplantation (alloHSCT). This approval marks a significant advancement for adult and pediatric patients, one year of age and older, suffering from acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS).
GRAFAPEX has been granted Orphan Drug Designation, which provides a seven-year period of regulatory exclusivity. Medexus Pharmaceuticals holds exclusive commercial rights to GRAFAPEX in the United States through a licensing agreement with medac GmbH.
Clinical Efficacy and Safety
The FDA's decision was supported by data from the MC-FludT.14/L Trial II (NCT00822393), a randomized, active-controlled study comparing treosulfan to busulfan, both in combination with fludarabine, as a preparative regimen for alloHSCT. The trial involved 570 patients with AML or MDS, aged 18 to 70 years, with specific performance status and comorbidity index criteria.
The primary efficacy outcome was overall survival (OS). The hazard ratio for OS in the randomized population was 0.67 (95% CI: 0.51, 0.90) compared to busulfan. Subgroup analyses showed hazard ratios of 0.73 (95% CI: 0.51, 1.06) in AML patients and 0.64 (95% CI: 0.40, 1.02) in MDS patients.
The most common adverse reactions (≥20%) included musculoskeletal pain, stomatitis, pyrexia, nausea, edema, infection, and vomiting. Grade 3 or 4 nonhematological laboratory abnormalities included increased GGT, bilirubin, ALT, AST, and creatinine.
Dosing and Administration
The recommended dose of treosulfan is 10 g/m2 daily on days -4, -3, and -2, combined with fludarabine 30 mg/m2 daily on days -6, -5, -4, -3, and -2, followed by alloHSCT on day 0.
Market and Financial Projections
Medexus anticipates launching GRAFAPEX in the first half of calendar year 2025. The company projects annual product-level revenue in the United States could exceed US$100 million within five years after commercial launch.
Ken d'Entremont, Medexus's Chief Executive Officer, stated, "Not only will GRAFAPEX make a substantial contribution to alloHSCT in the United States, but it also solidifies Medexus's leadership position in this therapeutic field."
Milestone Payments
Medexus will pay medac a regulatory milestone amount of $15 million based on the FDA-approved product label. The amount is payable in installments, with US$2.5 million by June 30, 2025, US$5 million by October 1, 2025, and US$7.5 million by January 1, 2026.
