Glasdegib

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Glasdegib
Glasdegib.svg
Names
Trade namesDaurismo
Other namesPF-04449913
  • 1-[(2R,4R)-2-(1H-Benzimidazol-2-yl)-1-methyl-4-piperidinyl]-3-(4-cyanophenyl)urea
Clinical data
Drug classHedgehog pathway inhibitor[1]
Main usesAcute myeloid leukemia (AML)[2]
Side effectsLow red blood cells, tiredness, bleeding, low white blood cells, pain, nausea, swelling, shortness of breath, altered taste, constipation, rash[3]
Pregnancy
category
  • US: N (Not classified yet)
Typical dose100 mg OD[1]
External links
AHFS/Drugs.comMonograph
US NLMGlasdegib
MedlinePlusa619004
Legal
Legal status
Chemical and physical data
FormulaC21H22N6O
Molar mass374.448 g·mol−1
3D model (JSmol)
  • CN1CCC(CC1C2=NC3=CC=CC=C3N2)NC(=O)NC4=CC=C(C=C4)C#N
  • InChI=1S/C21H22N6O/c1-27-11-10-16(24-21(28)23-15-8-6-14(13-22)7-9-15)12-19(27)20-25-17-4-2-3-5-18(17)26-20/h2-9,16,19H,10-12H2,1H3,(H,25,26)(H2,23,24,28)/t16-,19-/m1/s1
  • Key:SFNSLLSYNZWZQG-VQIMIIECSA-N

Glasdegib, sold under the brand name Daurismo, is a medication used to treat acute myeloid leukemia (AML).[2] It is used together with cytarabine in those who cannot tolerate intensive induction chemotherapy such as those over the age of 75.[3] It is taken by mouth.[3]

Common side effects include low red blood cells, tiredness, bleeding, low white blood cells, pain, nausea, swelling, shortness of breath, altered taste, constipation, and rash.[3] Other side effects include QT prolongation and infertility.[6] Use in pregnancy may harm the baby.[3] It is a hedgehog pathway inhibitor which blocks smoothened (SMO).[1][2]

Glasdegib was approved for medical use in the United States in 2018 and Europe in 2020.[6][2] In the United Kingdom it costs the NHS about £10,500 per month as of 2021.[1] This amount in the United States is about 19,500 USD and in Canada is about 17,200 CAD.[7][8]

Medical uses

Dosage

The recommended dose 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.[3]

History

Glasdegib was approved for medical use in the United States in December 2018.[9][3][10][11][12]

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.[9] 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.[9] The trial was conducted in United States, Canada and Europe.[13]

Efficacy was established based on an improvement in overall survival (date of randomization to death from any cause).[9] 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).[9]

Glasdegib was granted priority review and orphan drug designation by the U.S. Food and Drug Administration (FDA).[9][14] It was granted orphan drug designation by the European Medicines Agency (EMA) in October 2017.[15]

Glasdegib was approved for medical use in the European Union in June 2020.[5]

References

  1. 1.0 1.1 1.2 1.3 BNF 81: March-September 2021. BMJ Group and the Pharmaceutical Press. 2021. p. 1050. ISBN 978-0857114105.
  2. 2.0 2.1 2.2 2.3 "Daurismo". Archived from the original on 5 August 2020. Retrieved 3 December 2021.
  3. 3.0 3.1 3.2 3.3 3.4 3.5 3.6 "Daurismo- glasdegib tablet, film coated". DailyMed. 26 November 2019. Archived from the original on 2 July 2019. Retrieved 25 March 2020.
  4. "Glasdegib (Daurismo) Use During Pregnancy". Drugs.com. 14 December 2018. Archived from the original on 25 March 2020. Retrieved 25 March 2020.
  5. 5.0 5.1 "Daurismo EPAR". European Medicines Agency (EMA). 28 April 2020. Archived from the original on 5 August 2020. Retrieved 25 September 2020.
  6. 6.0 6.1 "Glasdegib Monograph for Professionals". Drugs.com. Archived from the original on 24 January 2021. Retrieved 3 December 2021.
  7. "Daurismo Prices, Coupons & Patient Assistance Programs". Drugs.com. Retrieved 3 December 2021.
  8. "Drug: Glasdegib (Daurismo)" (PDF). Archived (PDF) from the original on 15 May 2021. Retrieved 3 December 2021.
  9. 9.0 9.1 9.2 9.3 9.4 9.5 "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. Archived from the original on 25 March 2020. Retrieved 25 March 2020. Public Domain This article incorporates text from this source, which is in the public domain.
  10. "Drug Approval Package: Daurismo (glasdegib)". U.S. Food and Drug Administration (FDA). 17 December 2018. Archived from the original on 25 March 2020. Retrieved 25 March 2020.
  11. "Daurismo: FDA-Approved Drugs". U.S. Food and Drug Administration (FDA). Archived from the original on 27 August 2021. Retrieved 25 March 2020.
  12. Hoy SM (February 2019). "Glasdegib: First Global Approval". Drugs. 79 (2): 207–213. doi:10.1007/s40265-018-1047-7. PMID 30666593.
  13. "Drug Trial Snapshot: Daurismo". U.S. Food and Drug Administration (FDA). 21 November 2018. Archived from the original on 25 March 2020. Retrieved 25 March 2020. Public Domain This article incorporates text from this source, which is in the public domain.
  14. "Search Orphan Drug Designations and Approvals". U.S. Food and Drug Administration (FDA). 24 December 1999. Archived from the original on 31 October 2021. Retrieved 25 March 2020.
  15. "EU/3/17/1923". European Medicines Agency (EMA). 17 September 2018. Archived from the original on 25 March 2020. Retrieved 25 March 2020.

External links

External sites:
Identifiers: