Treosulfan Regimen Approved for Allo-HSCT Conditioning in AML/MDS

The FDA approved treosulfan (Grafapex; Medexus Pharma) plus fludarabine (Fludara; Bayer HealthCare Pharmaceuticals) as a conditioning regimen for allogeneic hematopoietic stem cell transplantation (allo-HSCT) in adult and pediatric patients aged 1 year and older with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS), Medexus Pharma announced in a press release.1

FDA approved. | Image Credit: Pawel - stock.adobe.com

The approval comes after a 3-month extension that set an FDA action date of January 30, 2025.2 Medexus is aiming for a commercial launch in the first half of 2025, according to the press release.1

Treosulfan was assessed in combination with fludarabine in the randomized, active-controlled MC-FludT.14/L Trial II (NCT00822393),3 with a main outcome of overall survival (OS). The study compared treosulfan-based conditioning with reduced-intensity busulfan-based conditioning in patients with AML or MDS at increased risk for standard conditioning therapies.

A total of 570 patients with AML or MDS were randomized to receive treosulfan (n = 280) or busulfan (n = 290) as allo-HSCT conditioning, and those in the overall randomized population who received treosulfan experienced better OS outcomes compared with busulfan (HR for OS, 0.67; 95% CI, 0.51-0.90).1 Among patients with AML, the HR was 0.73 (95% CI, 0.51-1.06), and the HR was 0.64 (95% CI, 0.40-1.02) among patients with MDS treated with treosulfan.

The most common adverse events that occurred in more than 20% of patients were musculoskeletal pain, stomatitis, pyrexia, nausea, edema, infection, and vomiting. Certain grade 3 or 4 nonhematological laboratory abnormalities were higher with treosulfan, including increased gamma-glutamyl transferase, bilirubin, alanine aminotransferase, aspartate aminotransferase, and creatinine.

"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 physician-scientist and principal investigator in clinical trials using treosulfan as part of a conditioning regimen, said in a statement.

References

1. Medexus announces FDA approval of Grafapex (treosulfan) for injection and provides business update. News release. Medexus. January 22, 2025. Accessed January 23, 2025. https://www.medexus.com/en_US/investors/news-events/press-releases/detail/176/medexus-announces-fda-approval-of-grafapex-treosulfan-for

2. Medexus provides update on treosulfan NDA review process and extended PDUFA goal date. News release. Medexus. September 16, 2024. Accessed January 23, 2025. https://www.medexus.com/en_US/investors/news-events/press-releases/detail/169/medexus-provides-update-on-treosulfan-nda-review-process

3. ClinicalTrials.gov. Clinical phase III trial treosulfan-based conditioning versus reduced-intensity conditioning (RIC). National Library of Medicine. Updated July 30, 2020. Accessed January 23, 2025. https://clinicaltrials.gov/study/NCT00822393