Glasdegib (Daurismo) — Clinical FAQs

Question 1

What is Glasdegib FDA-approved to treat?

Accepted Answer

Glasdegib is FDA-approved for the following oncology indications: 1. Newly diagnosed acute myeloid leukemia (AML) or AML with myelodysplasia-related changes in adults aged ≥75 years or who have comorbidities that preclude use of intensive induction chemotherapy — in combination with low-dose cytarabine (LDAC) (FDA approved November 2018; based on the BRIGHT AML 1003 trial).

Question 2

How does Glasdegib work (mechanism of action)?

Accepted Answer

Glasdegib is an orally bioavailable, selective inhibitor of Smoothened (SMO), a key transmembrane signal transducer of the Hedgehog (Hh) signaling pathway. Under normal conditions, Hedgehog ligand binding to Patched-1 (PTCH1) relieves PTCH1-mediated inhibition of SMO, allowing SMO to initiate an intracellular cascade driving nuclear translocation of GLI transcription factors (GLI1, GLI2) and transcription of target genes governing cell survival, proliferation, and self-renewal. In AML, aberrant Hh/GLI pathway activation is implicated in the maintenance and expansion of leukemic stem cells. Glasdegib binds the heptahelical bundle of SMO, locking it in an inactive conformation and preventing downstream GLI-mediated transcription. Preclinical studies show SMO inhibition reduces leukemic stem cell frequency and synergizes with the prodifferentiating effects of low-dose cytarabine (LDAC), providing mechanistic rationale for the combination.

Question 3

How is Glasdegib administered?

Accepted Answer

Glasdegib is administered Oral (PO). Glasdegib 100 mg PO once daily on days 1–28 of each 28-day cycle (continuous dosing), in combination with LDAC 20 mg SC twice daily on days 1–10 of each cycle.

Question 4

What are the most common side effects of Glasdegib?

Accepted Answer

The most commonly reported side effects of Glasdegib (≥10% incidence) include: Anemia (74%, all grade), Fatigue (68%), Hemorrhage (42%), Febrile neutropenia (34%), Edema (35%) and others (19 total). Consult your oncologist for complete prescribing information.

Question 5

Does Glasdegib have a black box warning?

Accepted Answer

Yes. Glasdegib carries FDA black box warning(s) regarding: 1. Embryo-fetal toxicity: Glasdegib can cause fetal harm based on mechanism of action (Hh pathway inhibition is essential for normal embryogenesis) and animal reproduction studies demonstrating embryolethality and teratogenicity (skeletal anomalies, exencephaly) at exposures below the human clinical dose. Verify pregnancy status before initiation in females of reproductive potential. Advise females to use effective contraception during treatment and for at least 30 days after the final dose. Advise males with female partners of reproductive potential to use effective contraception during treatment and for at least 30 days after the last dose. 2. QTc prolongation: Glasdegib prolongs the QTc interval in a concentration-dependent manner and can cause life-threatening arrhythmias including torsades de pointes. Obtain a 12-lead ECG before initiating glasdegib and monitor periodically. Correct hypokalemia and hypomagnesemia before and throughout treatment. Avoid concomitant QTc-prolonging medications. Withhold glasdegib for QTc ≥481 ms.

Question 6

Is Glasdegib safe during pregnancy?

Accepted Answer

Glasdegib pregnancy safety: Causes fetal harm (no traditional FDA letter category under current labeling). Glasdegib is embryotoxic and teratogenic in animals at exposures below the human clinical dose based on Hh pathway-dependent embryogenesis. Pregnancy must be excluded before initiation. Females of reproductive potential must use effective contraception during treatment and for ≥30 days after the last dose; males with female partners of reproductive potential must also use contraception. Breastfeeding should be discontinued during therapy and for at least 30 days after the final dose.. Oncologists should review the complete prescribing information and discuss reproductive risks with patients before initiating therapy.

Glasdegib — Drug Monograph

Mechanism of Action

FDA Indications

Common Side Effects

Clinical Pearl

Related Therapies & Mechanisms