{{Short description|Treatment for acute myeloid leukemia}} {{Infobox drug | image = Glasdegib.svg | image_class = skin-invert-image | alt = | caption =
<!-- Clinical data --> | pronounce = | tradename = Daurismo | Drugs.com = {{drugs.com|monograph|glasdegib-maleate}} | MedlinePlus = a619004 | pregnancy_AU = <!-- A/B1/B2/B3/C/D/X --> | pregnancy_AU_comment = | routes_of_administration = | class = | ATCvet = | ATC_prefix = L01 | ATC_suffix = XJ03
| legal_AU = <!-- S2, S3, S4, S5, S6, S7, S8, S9 or Unscheduled--> | legal_AU_comment = | legal_CA = Rx-only | legal_CA_comment = <ref>{{Cite web |date=23 October 2014 |title=Summary Basis of Decision (SBD) for Daurismo |url=https://hpr-rps.hres.ca/reg-content/summary-basis-decision-detailTwo.php?linkID=SBD00483&lang=en |access-date=29 May 2022 |website=Health Canada}}</ref> | legal_DE = <!-- Anlage I, II, III --> | legal_NZ = <!-- Class A, B, C --> | legal_UK = <!-- GSL, P, POM, CD, CD Lic, CD POM, CD No Reg POM, CD (Benz) POM, CD (Anab) POM or CD Inv POM / Class A, B, C --> | legal_US = Rx-only | legal_EU = Rx-only | legal_EU_comment = <ref name="Daurismo EPAR">{{Cite web |date=28 April 2020 |title=Daurismo EPAR |url=https://www.ema.europa.eu/en/medicines/human/EPAR/daurismo |access-date=25 September 2020 |website=European Medicines Agency (EMA)}}</ref><ref>{{Cite web |title=Daurismo Product information |url=https://ec.europa.eu/health/documents/community-register/html/h1451.htm |access-date=3 March 2023 |website=Union Register of medicinal products}}</ref> | legal_UN = <!-- N I, II, III, IV / P I, II, III, IV--> | legal_status = <!-- Free text -->
<!-- Pharmacokinetic data --> | bioavailability = | protein_bound = | metabolism = | metabolites = | onset = | elimination_half-life = | duration_of_action = | excretion =
<!-- Identifiers --> | index2_label = as salt | CAS_number = 1095173-27-5 | PubChem = 25166913 | DrugBank = DB11978 | UNII_Ref = {{fdacite|correct|FDA}} | UNII = K673DMO5H9 | KEGG_Ref = {{keggcite|correct|kegg}} | KEGG = D10636 | KEGG2_Ref = {{keggcite|correct|kegg}} | KEGG2 = D11107 | ChemSpiderID = 28518072 | ChEBI = 145428 | ChEMBL = 2043437 | synonyms = PF-04449913
<!-- Chemical and physical data --> | IUPAC_name = 1-[(2''R'',4''R'')-2-(1''H''-Benzimidazol-2-yl)-1-methyl-4-piperidinyl]-3-(4-cyanophenyl)urea | C=21|H=22|N=6|O=1 | SMILES = CN1CCC(CC1C2=NC3=CC=CC=C3N2)NC(=O)NC4=CC=C(C=C4)C#N | StdInChI=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 | StdInChIKey=SFNSLLSYNZWZQG-VQIMIIECSA-N }}
'''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.<ref name="FDA PR">{{Cite press release |title=FDA approves glasdegib for AML in adults age 75 or older or who have comorbidities |date=21 November 2018 |url=http://www.fda.gov/drugs/fda-approves-glasdegib-aml-adults-age-75-or-older-or-who-have-comorbidities |archive-url=https://web.archive.org/web/20190928084034/https://www.fda.gov/drugs/fda-approves-glasdegib-aml-adults-age-75-or-older-or-who-have-comorbidities |url-status=dead |archive-date=September 28, 2019 |access-date=25 March 2020 |website=U.S. Food and Drug Administration (FDA)}} {{PD-notice}}</ref><ref name="Daurismo FDA label">{{Cite web |date=26 November 2019 |title=Daurismo- glasdegib tablet, film coated |url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=204a6f7e-c9a4-472b-abd2-9527bda64d17 |access-date=25 March 2020 |website=DailyMed}}</ref><ref name="pmid32027196">{{Cite journal |vauthors=Thomas X, Heiblig M |date=April 2020 |title=An evaluation of glasdegib for the treatment of acute myelogenous leukemia |journal=Expert Opinion on Pharmacotherapy |volume=21 |issue=5 |pages=523–530 |doi=10.1080/14656566.2020.1713094 |pmid=32027196 |s2cid=211044663}}</ref> It is taken by mouth and is used in combination with low-dose cytarabine.<ref name="Daurismo FDA label" />
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.<ref name="Daurismo FDA label" />
The most common adverse reactions are anemia, fatigue, hemorrhage, febrile neutropenia, musculoskeletal pain, nausea, edema, thrombocytopenia, dyspnea, decreased appetite, dysgeusia, mucositis, constipation, and rash.<ref name="FDA PR" />
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.<ref>{{Cite web |title=Glasdegib - AdisInsight |url=http://adisinsight.springer.com/drugs/800030686 |access-date=2017-05-22 |publisher=Adisinsight.springer.com}}</ref>
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==History== Glasdegib was approved for medical use in the United States in December 2018.<ref name="FDA PR" /><ref name="Daurismo FDA label" /><ref>{{Cite web |date=17 December 2018 |title=Drug Approval Package: Daurismo (glasdegib) |url=https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210656Orig1s000TOC.cfm |access-date=25 March 2020 |website=U.S. Food and Drug Administration (FDA)}}</ref><ref>{{Cite web |title=Daurismo: FDA-Approved Drugs |url=https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=BasicSearch.process |archive-url=https://web.archive.org/web/20240731125622/https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=BasicSearch.process |url-status=dead |archive-date=July 31, 2024 |access-date=25 March 2020 |website=U.S. Food and Drug Administration (FDA)}}</ref><ref name="pmid30666593">{{Cite journal |vauthors=Hoy SM |date=February 2019 |title=Glasdegib: First Global Approval |journal=Drugs |volume=79 |issue=2 |pages=207–213 |doi=10.1007/s40265-018-1047-7 |pmid=30666593 |s2cid=58541521}}</ref>
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.<ref name="FDA PR" /> 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.<ref name="FDA PR" /> The trial was conducted in United States, Canada and Europe.<ref name="FDA snapshot">{{Cite web |date=21 November 2018 |title=Drug Trial Snapshot: Daurismo |url=http://www.fda.gov/drugs/drug-approvals-and-databases/drug-trial-snapshot-daurismo |access-date=25 March 2020 |website=U.S. Food and Drug Administration (FDA)}}{{dead link|date=May 2025|bot=medic}}{{cbignore|bot=medic}} {{PD-notice}}</ref>
Efficacy was established based on an improvement in overall survival (date of randomization to death from any cause).<ref name="FDA PR" /> 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).<ref name="FDA PR" />
Glasdegib was granted priority review and orphan drug designation by the U.S. Food and Drug Administration (FDA).<ref name="FDA PR" /><ref>{{Cite web |date=24 December 1999 |title=Search Orphan Drug Designations and Approvals |url=https://www.accessdata.fda.gov/scripts/opdlisting/oopd/detailedIndex.cfm?cfgridkey=585517 |access-date=25 March 2020 |website=U.S. Food and Drug Administration (FDA)}}</ref> It was granted orphan drug designation by the European Medicines Agency (EMA) in October 2017.<ref>{{Cite web |date=17 September 2018 |title=EU/3/17/1923 |url=https://www.ema.europa.eu/en/medicines/human/orphan-designations/eu3171923 |access-date=25 March 2020 |website=European Medicines Agency (EMA)}}</ref>
Glasdegib was approved for medical use in the European Union in June 2020.<ref name="Daurismo EPAR" />
== References == {{reflist}}
==External links== * {{ClinicalTrialsGov|NCT01546038|A Study To Evaluate PF-04449913 With Chemotherapy In Patients With Acute Myeloid Leukemia or Myelodysplastic Syndrome}}
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