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| Clinical data | |
|---|---|
| Trade names | Daurismo |
| Other names | PF-04449913 |
| AHFS/Drugs.com | Monograph |
| MedlinePlus | a619004 |
| ATC code | |
| Legal status | |
| Legal status | |
| Identifiers | |
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| CAS Number | |
| PubChemCID | |
| DrugBank | |
| ChemSpider | |
| UNII | |
| KEGG | |
| ChEBI | |
| ChEMBL | |
| CompTox Dashboard(EPA) | |
| ECHA InfoCard | 100.244.738 |
| Chemical and physical data | |
| Formula | C21H22N6O |
| Molar mass | 374.448 g·mol−1 |
| 3D model (JSmol) | |
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Glasdegib, sold under the brand nameDaurismo, is a medication for the treatment of newly diagnosed acute myeloid leukemia (AML) in adults older than 75 years or those who have comorbidities that preclude use of intensive inductionchemotherapy.[4][5][6] It is taken by mouth and is used in combination with low-dosecytarabine.[5]
The recommended dose of glasdegib is 100 mg orally once daily on days 1 to 28 in combination with cytarabine 20 mg subcutaneously twice daily on days 1 to 10 of each 28-day cycle in the absence of unacceptable toxicity or loss of disease control.[5]
The most common adverse reactions are anemia, fatigue, hemorrhage, febrile neutropenia, musculoskeletal pain, nausea, edema, thrombocytopenia, dyspnea, decreased appetite, dysgeusia, mucositis, constipation, and rash.[4]
It is a small molecule inhibitor ofsonic hedgehog, which is a protein overexpressed in many types of cancer. It inhibits the sonic hedgehog receptorsmoothened (SMO), as do most drugs in its class.[7]
Glasdegib was approved for medical use in the United States in December 2018.[4][5][8][9][10]
FDA approval was based on a multicenter, open-label, randomized study (BRIGHT AML 1003, NCT01546038) that included 115 subjects with newly diagnosed AML who met at least one of the following criteria: a) age 75 years or older, b) severe cardiac disease, c) baseline Eastern Cooperative Oncology Group performance status of 2, or d) baseline serum creatinine >1.3 mg/dL.[4] Subjects were randomized 2:1 to receive glasdegib, 100 mg daily, with LDAC 20 mg subcutaneously twice daily on days 1 to 10 of a 28-day cycle (N=77) or LDAC alone (N=38) in 28-day cycles until disease progression or unacceptable toxicity.[4] The trial was conducted in United States, Canada and Europe.[11]
Efficacy was established based on an improvement in overall survival (date of randomization to death from any cause).[4] With a median follow-up of 20 months, median survival was 8.3 months (95% CI: 4.4, 12.2) for the glasdegib + LDAC arm and 4.3 months (95% CI: 1.9, 5.7) for the LDAC alone arm and HR of 0.46 (95% CI: 0.30, 0.71; p=0.0002).[4]
Glasdegib was grantedpriority review andorphan drug designation by the U.S.Food and Drug Administration (FDA).[4][12] It was grantedorphan drug designation by theEuropean Medicines Agency (EMA) in October 2017.[13]
Glasdegib was approved for medical use in the European Union in June 2020.[2]
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