FDA Approves First and Only Hedgehog Pathway Inhibitor for AML Treatment

The Food and Drug Administration (FDA) approved Daurismo (glasdegib) plus low-dose cytarabine (LDAC) chemotherapy to treat newly diagnosed patients with acute myeloid leukemia (AML) who are 75 years or older and have other health issues or chronic diseases that make them ineligible for treatment with chemotherapy.

The approval was based off a randomized phase 2 clinical trial that included more than 100 patients who were randomized to receive either Daurismo plus LDAC or LDAC alone. The Daurismo arm had an average overall survival of 8.3 months compared with 4.3 months for those who only received LDAC. This difference represented a 54 percent reduction in the risk of death for patients treated with the combination.

“Intensive chemotherapy is usually used to control AML, but many adults with AML are unable to have intensive chemotherapy because of its toxicities. Today’s approval gives health care providers another tool to use in the treatment of AML patients with various, unique needs. Clinical trials showed that overall survival was improved using Daurismo in combination with LDAC compared to LDAC alone for patients who would not tolerate intensive chemotherapy,” said Richard Pazdur, M.D., director of the FDA’s Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research, in a statement.

Prescribing information for Daurismo includes a warning regarding embryo-fetal death or severe birth defects, so the drug should not be used in women who are pregnant or breastfeeding. Other common side effects observed in the clinical trial included anemia, fatigue, hemorrhage, febrile neutropenia, muscle pain, nausea, swelling in the arms and legs, thrombocytopenia, shortness of breath, decreased appetite, distorted taste, pain or sores in mouth, constipation and rash.

The approval of Daurismo — the first and only Hedgehog pathway inhibitor for this indication – is coming after a June 2018 priority review for the drug.