FDA Approves Grafapex (Treosulfan) for HSCT Conditioning

The US Food and Drug Administration (FDA) has approved treosulfan (Grafapex, Medexus Pharmaceuticals) in combination with fludarabine as a preparative regimen to clear bone marrow before allogeneic hematopoietic stem cell transplant in adults and children with acute myeloid leukemia or myelodysplastic syndromes who are at increased risk for adverse events with standard conditioning regimens. 

In a June 2024 press release, a Medexus executive said the company is “optimistic” that treosulfan will become the new “gold standard” in the United States for the indication “as it [is now] in Europe and Canada,” where the alkylating agent is already on the market.

Approval in the United States was delayed for several years pending FDA’s request for additional information regarding treosulfan’s pivotal phase 3 trial, dubbed MC-FludT.14/L. 

The trial included European adults (median age, 60 years) with acute myeloid leukemia or myelodysplastic syndromes undergoing transplant. They were randomly assigned about equally to intravenous (IV) fludarabine with either treosulfan at 30 g/m² IV or busulfan at 6.4 mg/kg IV, which is a reduced-intensity dose of busulfan widely used in older patients or in those with comorbidity.

Event-free survival at 36 months was 59.5% with treosulfan vs 49.7% with busulfan (HR, 0.64; 95% CI, 0.49-0.84; P = .0006); 36-month overall survival was 66.8% in the treosulfan group vs 56.3% (HR, 0.64; 95% CI, 0.48-0.87; P =  .0037). Similar benefits with treosulfan vs busulfan have been reported in children. 

Adverse events in more than 10% of adults with treosulfan conditioning include nausea, stomatitis, vomiting, diarrhea, elevated bilirubin, fatigue, infections, and febrile neutropenia. Adverse events in more than 10% of children include stomatitis, vomiting, diarrhea, nausea, abdominal pain, hepatotoxicity, pyrexia, infections, elevated alanine aminotransferase, alopecia, and pruritus.

The phase 3 trial reported equal distribution of such adverse events between the treosulfan and busulfan study arms. 

Medexus anticipates that US sales of treosulfan could top $100 million within 5 years.

M. Alexander Otto is a physician assistant with a master’s degree in medical science and a journalism degree from Newhouse. He is an award-winning medical journalist who worked for several major news outlets before joining Medscape. Alex is also an MIT Knight Science Journalism fellow. Email:aotto@mdedge.com