Daurismo Combo Approved in Europe for Select Adults With AML

Daurismo Combo Approved in Europe for Select Adults With AML

Pfizer announced that the European Commission has approved Daurismo (glasdegib) in combination with low-dose cytarabine to treat newly diagnosed acute myeloid leukemia (AML) among adults who are not candidates for standard chemotherapy.

The approval followed a favorable opinion from the Committee for Medicinal Products for Human Use, a branch of the European Medicines Agency. This opinion was based upon the results of Pfizer’s Phase 2 BRIGHT 1003 trial (NCT01546038) and the medicine’s approval by the U.S. Food and Drug Administration in 2018.

Daurismo is a once-daily oral medication that inhibits the Hedgehog pathway, a biological process important for cellular differentiation and proliferation. This pathway is often dysregulated in cancers, which can underlie much of the aberrant growth and proliferation seen in cancer cells.

In the U.S. and Canada, Daurismo plus low-dose cytarabine (LDAC) is approved to treat newly diagnosed AML in adults age 75 or older, or who have comorbidities (simultaneously occurring conditions) that preclude intensive chemotherapy.

The BRIGHT study evaluated the efficacy of Daurismo in combination with chemotherapy, versus chemotherapy alone, in patients with previously untreated de novo or secondary AML who were ineligible for intensive chemotherapy.

De novo AML occurs when there is no prior history of myelodysplastic syndromes (MDS), myeloproliferative disorder, or exposure to potential leukemia-causing agents. Secondary AML develops as a result of prior blood or bone marrow conditions or previous anticancer therapy.

Of the 78 patients given the Daurismo and LDAC combination therapy, 40 had secondary AML and 11 of these had been previously treated with a hypomethylating agent. Historically, these patients have poor prognoses and treatment is often limited to experimental agents in clinical trials or to palliative care.

“The standard of care for people with acute myeloid leukemia is intensive chemotherapy, however, this is not an option for many elderly people and those who have certain health conditions prior to receiving their diagnosis,” said Masum Hossain, Regional President at Pfizer, in a company press release.

“Through the European Commission approval of Daurismo, we are proud to further deliver on our decades long commitment to people living with blood cancers by offering this new treatment option for certain patients in Europe with acute myeloid leukemia, who previously had limited treatment options.”

Daurismo nearly doubled patients’ median overall survival, to 8.3 months, from 4.3 months for those taking LDAC alone. This translated to a 54% reduction in the risk of death for those given both Daurismo and LDAC.

“The BRIGHT 1003 trial demonstrated that Daurismo in combination with low-dose cytarabine nearly doubled overall survival compared to low-dose cytarabine alone,” said Pau Montesinos, MD, of the University Hospital La Fe in Valencia, Spain, one of the trials testing sites. “People with previously untreated acute myeloid leukemia who cannot withstand intensive chemotherapy are in urgent need of new options and I look forward to using this new therapy that may extend survival for appropriate patients.”

The most frequently reported adverse reactions included nausea, loss of appetite, fatigue, and muscle spasms. Muscle spasms and fatigue, as well as febrile neutropenia (a low white blood cell count during a fever), anemia, thrombocytopenia (low platelet count), and electrocardiogram anomalies were the adverse reactions most associated with reductions in dosage.

Among people on the combination treatment who left the study, 5.9% discontinued due to pneumonia, 3.5% for febrile neutropenia, and 2.3% due to nausea.