FDA Fast Track designation granted to devimistat for the treatment of AML

On December 15, 2020, it was announced that the U.S. Food and Drug Administration (FDA) granted Fast Track designation to devimistat, a lipoate analog, for the treatment of acute myeloid leukemia (AML). The efficacy and safety of devimistat is currently being evaluated in the pivotal phase III ARMADA 2000 trial (NCT03504410) in combination with high dose cytarabine (HiDAC) + mitoxantrone.^1-3   

Devimistat^1,2

• First-in-class lipoate analog that inhibits pyruvate dehydrogenase and alpha-ketoglutarate dehydrogenase and therefore stops the mitochondrial tricarboxylic acid cycle in cancerous cells, leading to cell death²
• Increases the sensitivity to other chemotherapeutic agents, allowing for potential combinations that could reduce the cytotoxicity and other side effects of chemotherapeutics
• Previously received Fast Track designation for the treatment of metastatic pancreatic cancer
• Previously received orphan drug designation by the FDA, for the treatment of AML, myelodysplastic syndromes, peripheral T-cell lymphoma and Burkitt’s lymphoma, pancreatic cancer, and soft tissue sarcoma; and by the European Medicines Agency (EMA) for AML and pancreatic cancer

ARMADA 2000 (NCT03504410)³

• Multicenter, open-label, phase III study of devimistat in combination with HiDAC + mitoxantrone in comparison with HiDAC + mitoxantrone and control combination sub-groups: mitoxantrone, etoposide, and cytarabine (MEC) and fludarabine, cytarabine, and filgrastim (FLAG) in older patients (≥ 50 years) with relapsed/refractory AML
• Start Date: November 12, 2018
• Estimated enrollment: 500
• Primary outcome: Complete remission
• Secondary outcomes: Overall survival, complete remission + complete remission with partial hematologic recovery

The Fast Track designation of this compound, particularly during a pandemic, highlights the need for new treatment options in the relapsed/refractory AML setting.