U.S. FDA Approves Pfizer’s DAURISMO™ (GLASDEGIB) For Adult Patients With Newly-Diagnosed Acute Myeloid Leukemia (AML)

Pfizer Inc. today announced that the U.S. Food and Drug Administration (FDA) approved 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. “We are proud to now offer these patients for whom intensive chemotherapy is not an option a new oral medicine, taken in combination with low-dose chemotherapy, that may improve their chances of survival.”

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

“The randomized Phase 2 study, which formed the basis for today’s approval, included patients with cardiac disease or mild to moderate kidney disease, who are often excluded from clinical trials,” said Jorge Cortes, M.D., deputy chair and professor of medicine in the Department of Leukemia, University of Texas, MD Anderson Cancer Center. “In the trial, DAURISMO plus low-dose chemotherapy reduced the risk of death during the study period by 54 percent compared to chemotherapy alone. This provides a much-needed treatment for those patients for whom intensive chemotherapy is not an option.”

In the pivotal, randomized, international Phase 2 BRIGHT 1003 trial, 115 patients with newly diagnosed AML were randomized 2:1 to receive DAURISMO plus LDAC or LDAC alone. Of the 77 patients treated with DAURISMO plus LDAC, more than half (51%, 39 patients) had secondary AML, or AML that develops as a result of prior blood/bone marrow conditions or previous anticancer therapy. Eleven of the 39 patients with secondary AML received prior treatment with a hypomethylating agent; historically, the prognosis is poor for these patients and treatment options have been limited to clinical trials or palliative care. Median overall survival was 8.3 months (95% CI: 4.4,12.2) for patients treated with DAURISMO plus LDAC compared with 4.3 months (95% CI: 1.9, 5.7) for patients treated with LDAC alone. This difference represented a 54 percent reduction in the risk of death for patients treated with DAURISMO plus LDAC (HR: 0.46, 95% CI: 0.30, 0.71, one-sided p-value 0.0002).1

The U.S. labeling for DAURISMO includes a boxed warning for embryo-fetal toxicity. The most frequently (≥20% of patients) reported adverse events (AEs) in patients treated with DAURISMO plus LDAC compared to LDAC alone in first 90 days of therapy were anemia (43% vs 42%), fatigue (36% vs 32%), hemorrhage (36% vs 42%), febrile neutropenia (31% vs 22%), musculoskeletal pain (30% vs 17%), nausea (29% vs 12%), edema (30% vs 20%), thrombocytopenia (30% vs 27%), dyspnea (23% vs 24%), decreased appetite (21% vs 7%), dysgeusia (21% vs 2%), mucositis (21% vs 12%), constipation (20% vs 12%) and rash (20% vs 7%).1 Serious adverse reactions were reported in 79% of patients treated in the DAURISMO plus LDAC arm. The most common (≥5%) serious adverse reactions in patients receiving DAURISMO plus LDAC were febrile neutropenia (29%), pneumonia (23%), hemorrhage (12%), anemia (7%) and sepsis (7%).1

“DAURISMO, a Hedgehog pathway inhibitor, was discovered in Pfizer laboratories and exemplifies our continued commitment to developing medicines that have the potential to advance cancer therapeutics,” said Mace Rothenberg, M.D., Chief Development Officer, Oncology, Pfizer Global Product Development. “We are delighted by today’s approval of DAURISMO by the FDA, and are working to gain greater understanding of its role in treating patients with acute myeloid leukemia. The ongoing Phase 3 BRIGHT trials are evaluating DAURISMO in combination with other agents commonly used to treat patients with acute myeloid leukemia, in an effort to understand the full potential of this medicine against this aggressive leukemia.”

Pfizer is committed to ensuring that patients who are prescribed DAURISMO have access to this innovative therapy. Patients in the U.S. have access to Pfizer Oncology Together™, which offers personalized support and financial assistance resources to help patients access their prescribed Pfizer Oncology medications.

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Related Topics and Keywords

Acute Myeloid Leukemia, AML, DAURISMO, GLASDEGIB, Pfizer