FDA Approves GRAFAPEX/Fludarabine Before alloHSCT in AML and MDS

The FDA approved GRAFAPEX and fludarabine as a preparative regimen in acute myeloid leukemia or myelodysplastic syndrome prior to alloHSCT.

The Food and Drug Administration (FDA) has approved GRAFAPEX™ (treosulfan), an alkylating agent, with fludarabine as a preparative regimen for adult and pediatric patients one year of age and older with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) receiving allogeneic hematopoietic stem cell transplantation (alloHSCT), according to a press release from Medexus Pharmaceuticals, Inc.

The efficacy of the now-FDA-approved regimen was evaluated in the randomized, active-controlled phase 2 MC-FludT.14/L trial, which compared GRAFAPEX — in 280 patients — with busulfan — in 290 patients — as a preparative regimen for alloHSCT. The hazard ratio for overall survival (OS; stratified by donor type and risk group) for this treatment, when compared with busulfan, was 0.67 in the randomized population, 0.73 in patients with AML and 0.64 in patients with MDS.

Regarding safety, musculoskeletal pain, stomatitis, pyrexia, nausea, edema, infection and vomiting were the most common side effects to the treatment and occurred in 20% or more of patients enrolled onto the study. However, selected Grade 3 (severe) or 4 (life-threatening or disabling) nonhematological laboratory abnormalities including increase in GGT (gamma-glutamyl transferase), increase in bilirubin, increase in ALT (alanine aminotransferase), increase in AST (aspartate aminotransferase) and increase in creatinine, occurred in patients.

GRAFAPEX for injection holds Orphan Drug Designation, according to the press release, which means that the product will benefit from a seven- year period of regulatory exclusivity in the FDA-approved indication.

"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," Ken d'Entremont, Medexus's Chief Executive Officer, explained in the press release. "Not only will GRAFAPEXTM make a substantial contribution to alloHSCT in the United States, but it also solidifies Medexus's leadership position in this therapeutic field."

Patients were eligible for enrollment onto the MC-FludT.14/L study so long as they were between 18 and 70 years of age, presented with AML or MDS, had a Karnofsky performance status of 60% or greater and/or a hematopoietic cell transplantation comorbidity index score greater than 2. A total of 570 patients were randomized onto the clinical trial, with 280 patients receiving GRAFAPEX and 290 receiving busulfan, the press release explained.

OS, defined as the time from randomization until death from any cause, served as the investigation's major efficacy outcome measure.

Additionally, investigators based the MC-FludT.14/L study protocol on results of previous phase 1/2 trials which evaluated GRAFAPEX and fludarabine conditioning prior to alloHSCT.

"We are targeting a commercial launch in the first half of calendar year 2025, and given our recent experience in Canada we are very optimistic about the potential of GRAFAPEX in the U.S. market," Richard Labelle, Medexus's Chief Operating Officer, added in the same press release. "We anticipate that GRAFAPEXTM will have a meaningful impact on Medexus's total revenue and believe that annual product-level revenue in the United States has the potential to exceed US$100 million within five years after commercial launch."

Furthermore, the recommended dose of GRAFAPEX 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 hematopoietic stem cell infusion on day 0.

"This FDA approval provides a useful option for adult and pediatric patients, with the potential to enhance overall survival while minimizing side effects," Dr. Filippo Milano, a stem cell transplant physician-scientist and principal investigator in clinical trials using the agent, concluded in the release.

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