Based on trial results that showed glasdegib, an investigational oral smoothened inhibitor, nearly doubled overall survival (OS) in patients with previously untreated acute myeloid leukemia (AML), the FDA has granted the Pfizer drug a Priority Review.
Glasdegib, an investigational oral smoothened inhibitor for the treatment of adult patients with previously untreated acute myeloid leukemia (AML) in combination with low-dose chemotherapy (cytarabine), has been granted Priority Review designation.
The FDA made its decision based on results from a randomized phase 2 trial, which had found a 49.9% reduction in the risk of death for patients treated with glasdegib plus cytarabine compared with patients treated with cytarabine alone. The Prescription Drug User Fee Act (PDUFA) goal date for a decision by the FDA is in December 2018.
“Patients with acute myeloid leukemia who are ineligible for intensive chemotherapy are in critical need of new treatment options to improve their overall survival,” Mace Rothenberg, MD, chief development officer, Oncology, Pfizer Global Product Development, said in a statement.
The phase 2 BRIGHT 1003 study was a randomized, open-label, multicenter trial in which 88 patients received 100 mg daily of glasdegib with 20 mg of cytarabine twice daily, and 44 patients received cytarabine alone. The median overall survival (OS) was 8.8 months for patients treated with glasdegib, while the patients on cytarabine alone had a median OS of 4.9 months.
The phase 2 trial results were originally presented at the 58th American Society of Hematology Annual Meeting and Exposition.
After the phase 2 trial results, Jorge Cortes, MD, a researcher in the trial and deputy chair and professor of medicine in the Department of Leukemia at MD Anderson Cancer Center, explained that glasdegib works by disrupting the Hedgehog pathway, which is thought to play a role in the development of multiple types of cancer.
“The Hedgehog pathway is a compelling target in cancer research because of the ability to target and disrupt the root of the cancer, that is the cancer-originating cell,” Cortes said in a statement in December 2016. “As the first smoothened inhibitor to demonstrate clinical benefit in patients with AML and high-risk MDS [myelodysplastic syndrome] who were ineligible for intensive chemotherapy, these results with glasdegib provide hope that interfering with this pathway may lead to potential new treatment options for blood cancers that may improve patient outcomes.”
The most common serious adverse events were febrile neutropenia (29% of patients in the glasdegib arm vs 20% in the cytarabine alone arm) and pneumonia (21% vs 17%).