<abstract xmlns="http://www.w3.org/1999/xhtml">

<p>Numerous new emerging therapies, including oral targeted chemotherapies, have recently entered the therapeutic arsenal against acute myeloid leukemia (AML). The significant shift toward the use of these novel therapeutics, administered either alone or in combination with intensive or low-intensity chemotherapy, changes the prospects for the control of this disease, especially for elderly patients. Glasdegib, an oral Hedgehog pathway inhibitor, showed satisfactory response rates associated with moderate toxicity and less early mortality than standard induction regimens in this population. It was approved in November 2018 by the FDA and in June 2020 by the EMA for use in combination with low-dose cytarabine as a treatment of newly-diagnosed AML in patients aged ≥ 75 and/or unfit for intensive induction chemotherapy. The current paper proposes an extensive, up-to-date review of the preclinical and clinical development of glasdegib. Elements of its routine clinical use and the landscape of ongoing clinical trials are also stated.</p>
</abstract>

Numerous new emerging therapies, including oral targeted chemotherapies, have recently entered the therapeutic arsenal against acute myeloid leukemia (AML). The significant shift toward the use of these novel therapeutics, administered either alone or in combination with intensive or low-intensity chemotherapy, changes the prospects for the control of this disease, especially for elderly patients. Glasdegib, an oral Hedgehog pathway inhibitor, showed satisfactory response rates associated with moderate toxicity and less early mortality than standard induction regimens in this population. It was approved in November 2018 by the FDA and in June 2020 by the EMA for use in combination with low-dose cytarabine as a treatment of newly-diagnosed AML in patients aged ≥ 75 and/or unfit for intensive induction chemotherapy. The current paper proposes an extensive, up-to-date review of the preclinical and clinical development of glasdegib. Elements of its routine clinical use and the landscape of ongoing clinical trials are also stated.

Update on glasdegib in acute myeloid leukemia – broadening horizons of Hedgehog pathway inhibitors

Université de Montpellier ENSCM, UFR des Sciences Pharmaceutiques et Biologiques

Aix Marseille Univ, CNRS, ICR UMR 7273, Equipe Pharmaco-Chimie Radicalaire Faculté de Pharmacie

Acta Pharmaceutica

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Numerous new emerging therapies, including oral targeted chemotherapies, have recently entered the therapeutic arsenal against acute myeloid leukemia (AML)....

Update on glasdegib in acute myeloid leukemia – broadening horizons of Hedgehog pathway inhibitors

Publié en ligne: 30 août 2021

Pages: 9 - 34

Accepté: 26 janv. 2021

DOI: https://doi.org/10.2478/acph-2022-0007

Mots clés
glasdegib, PF-04449913, PF-913, acute myeloid leukemia, Hedgehog pathway, smoothened

© 2022 Cyril Fersing et al., published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Update on glasdegib in acute myeloid leukemia – broadening horizons of Hedgehog pathway inhibitors

Publié en ligne: 30 août 2021

Pages: 9 - 34

Accepté: 26 janv. 2021

DOI: https://doi.org/10.2478/acph-2022-0007

Mots clésglasdegib, PF-04449913, PF-913, acute myeloid leukemia, Hedgehog pathway, smoothened

© 2022 Cyril Fersing et al., published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Mots clés
glasdegib, PF-04449913, PF-913, acute myeloid leukemia, Hedgehog pathway, smoothened