The U.S. Food and Drug Administration (FDA) has approved Pfizer Inc.’s Daurismo (glasdegib), a once-daily oral medicine, for the treatment of newly diagnosed acute myeloid leukemia (AML) in adult patients who are 75 years or older or who have comorbidities that preclude use of intensive induction chemotherapy.
Daurismo is taken in combination with low-dose cytarabine (LDAC), a type of chemotherapy. Daurismo has not been studied in patients with severe renal impairment or moderate-to-severe hepatic impairment.1
AML is a rapidly progressing bone marrow cancer with poor survival rates compared to other leukemias.2 The standard of care for people with AML is intensive chemotherapy; however, for many elderly patients with AML, as well as those who have certain health conditions prior to receiving their diagnosis, intensive treatment is not an option.3 Historically, a majority of these individuals do not receive treatment and face a poor prognosis.4
“As our second medicine approved in the last 14 months for patients with acute myeloid leukemia, Daurismo reinforces our commitment to delivering new medicines to patients living with some of the most difficult-to-treat cancers, especially those for which there are limited treatment options available,” said Andy Schmeltz, global president, Pfizer Oncology.
Daurismo is the first and only FDA-approved Hedgehog pathway inhibitor for AML. The Hedgehog signaling pathway plays an essential role in embryogenesis, the process by which human embryos are developed.
In adults, however, abnormal activation of this pathway is thought to contribute to the development and persistence of cancer stem cells. Preclinical studies have shown that disruption of this pathway can impair the development and survival of these cancer stem cells.5,6
1 Daurismo (glasdegib) Prescribing Information. New York. NY: Pfizer Inc: 2018.
2 SEER Cancer Stat Facts: Acute Myeloid Leukemia. National Cancer Institute. Bethesda, MD, April 2017. Available at: http://seer.cancer.gov/statfacts/html/amyl.html. Accessed November 7, 2018.
3 Dohner H, Estey E, Grimwade D, et al. Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel. Blood. 2017;129:424-447.
4 Medeiros BC, Satram-Hoang S, Hurst D, Hoang KQ, Momin F, Reyes C. Big data analysis of treatment patterns and outcomes among elderly acute myeloid leukemia patients in the United States. Ann Hematol. 2015;94:1127-1138. doi:10.1007/s00277-015-2351-x.
5 Irvine DA, Copland M. Targeting hedgehog in hematologic malignancy. Blood. 2012;119(10):2196-2204. doi:10.1182/blood-2011-10-383752.
6 Laranjeira ABA, Yang SX. Therapeutic target discovery and drug development in cancer stem cells for leukemia and lymphoma: from bench to the clinic. Expert Opinion on Drug Discovery. 2016;11(11):1071-1080. doi:10.1080/17460441.2016.1236785.
(Source: Pfizer Inc.)