Glasdegib

Glasdegib

Glasdegib

Treatment for acute myeloid leukemia

Glasdegib, sold under the brand name Daurismo, 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 induction chemotherapy.[5][6][7] It is taken by mouth and is used in combination with low-dose cytarabine.[6]

Quick Facts Clinical data, Trade names ...

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.[6]

The most common adverse reactions are anemia, fatigue, hemorrhage, febrile neutropenia, musculoskeletal pain, nausea, edema, thrombocytopenia, dyspnea, decreased appetite, dysgeusia, mucositis, constipation, and rash.[5]

It is a small molecule inhibitor of sonic hedgehog, which is a protein overexpressed in many types of cancer. It inhibits the sonic hedgehog receptor smoothened (SMO), as do most drugs in its class.[8]

History

Glasdegib was approved for medical use in the United States in December 2018.[5][6][9][10][11]

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.[5] 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.[5] The trial was conducted in United States, Canada and Europe.[12]

Efficacy was established based on an improvement in overall survival (date of randomization to death from any cause).[5] 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).[5]

Glasdegib was granted priority review and orphan drug designation by the U.S. Food and Drug Administration (FDA).[5][13] It was granted orphan drug designation by the European Medicines Agency (EMA) in October 2017.[14]

Glasdegib was approved for medical use in the European Union in June 2020.[3]

References

  1. [1]
    "Summary Basis of Decision (SBD) for Daurismo". Health Canada. 23 October 2014. Retrieved 29 May 2022.
  2. [2]
    "FDA-sourced list of all drugs with black box warnings (Use Download Full Results and View Query links.)". nctr-crs.fda.gov. FDA. Retrieved 22 Oct 2023.
  3. [3]
    "Daurismo EPAR". European Medicines Agency (EMA). 28 April 2020. Retrieved 25 September 2020.
  4. [4]
    "Daurismo Product information". Union Register of medicinal products. Retrieved 3 March 2023.
  5. [5]
    "FDA approves glasdegib for AML in adults age 75 or older or who have comorbidities". U.S. Food and Drug Administration (FDA) (Press release). 21 November 2018. Retrieved 25 March 2020. Public Domain This article incorporates text from this source, which is in the public domain.
  6. [6]
    "Daurismo- glasdegib tablet, film coated". DailyMed. 26 November 2019. Retrieved 25 March 2020.
  7. [7]
    Thomas X, Heiblig M (April 2020). "An evaluation of glasdegib for the treatment of acute myelogenous leukemia". Expert Opinion on Pharmacotherapy. 21 (5): 523–530. doi:10.1080/14656566.2020.1713094. PMID 32027196. S2CID 211044663.
  8. [8]
    "Glasdegib - AdisInsight". Adisinsight.springer.com. Retrieved 2017-05-22.
  9. [9]
    "Drug Approval Package: Daurismo (glasdegib)". U.S. Food and Drug Administration (FDA). 17 December 2018. Retrieved 25 March 2020.
  10. [10]
    "Daurismo: FDA-Approved Drugs". U.S. Food and Drug Administration (FDA). Retrieved 25 March 2020.
  11. [11]
    Hoy SM (February 2019). "Glasdegib: First Global Approval". Drugs. 79 (2): 207–213. doi:10.1007/s40265-018-1047-7. PMID 30666593. S2CID 58541521.
  12. [12]
    "Drug Trial Snapshot: Daurismo". U.S. Food and Drug Administration (FDA). 21 November 2018. Retrieved 25 March 2020. Public Domain This article incorporates text from this source, which is in the public domain.
  13. [13]
    "Search Orphan Drug Designations and Approvals". U.S. Food and Drug Administration (FDA). 24 December 1999. Retrieved 25 March 2020.
  14. [14]
    "EU/3/17/1923". European Medicines Agency (EMA). 17 September 2018. Retrieved 25 March 2020.
  • "Glasdegib". Drug Information Portal. U.S. National Library of Medicine.
  • Clinical trial number NCT01546038 for "A Study To Evaluate PF-04449913 With Chemotherapy In Patients With Acute Myeloid Leukemia or Myelodysplastic Syndrome" at ClinicalTrials.gov


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