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Drugs
Published in: Drugs 5/2019

01-04-2019 | Myelodysplastic Syndrome | AdisInsight Report

Tagraxofusp: First Global Approval

Author: Yahiya Y. Syed

Published in: Drugs | Issue 5/2019

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Abstract

Tagraxofusp (tagraxofusp-erzs) [Elzonris™] is an intravenously administered CD123-directed cytotoxin (composed of human interleukin-3 and a truncated diphtheria toxin payload) that was developed by Stemline Therapeutics, Inc. for the treatment of blastic plasmacytoid dendritic cell neoplasm (BPDCN). In December 2018, tagraxofusp received its first global approval in the USA for the treatment of BPDCN in adults and in paediatric patients aged 2 years and older. A centralized registration application for the use of tagraxofusp in patients with BPDCN is under review in the EU. This article summarizes the milestones in the development of tagraxofusp leading to its first global approval for the treatment of BPDCN.
Literature
1.
Frankel AE, Ramage J, Kiser M, et al. Characterization of diphtheria fusion proteins targeted to the human interleukin-3 receptor. Protein Eng. 2000;13(8):575–81.CrossRefPubMed
2.
Frankel AE, Woo JH, Ahn C, et al. Activity of SL-401, a targeted therapy directed to interleukin-3 receptor, in blastic plasmacytoid dendritic cell neoplasm patients. Blood. 2014;124(3):385–92.CrossRefPubMedPubMedCentral
3.
Pemmaraju N. Blastic plasmacytoid dendritic cell neoplasm. Clin Adv Hematol Oncol. 2016;14(4):220–3.PubMed
4.
5.
Stemline Therapeutics. Stemline Therapeutics announces that European Medicines Agency (EMA) grants accelerated assessment for planned Elzonris marketing authorization application (MAA) [media release]. 20 Nov 2018. http://​www.​stemline.​com.
6.
Stemline Therapeutics. Stemline Therapeutics receives breakthrough therapy designation from U.S. Food and Drug Administration for SL-401 [media release]. 23 Aug 2016. http://​www.​stemline.​com.
7.
Stemline Therapeutics. Stemline Therapeutics’ SL-401 receives orphan drug designation for the treatment of blastic plasmacytoid dendritic cell neoplasm (BPDCN) [media release]. 10 June 2013. http://​www.​stemline.​com.
8.
Stemline Therapeutics. Stemline Therapeutics receives orphan drug designation for SL-401 for the treatment of acute myeloid leukemia [media release]. 9 Mar 2011. http://​www.​stemline.​com.
9.
10.
Stemline Therapeutics. Stemline Therapeutics announces SL-401 receives EU orphan drug designation for treatment of acute myeloid leukemia (AML) [media release]. 10 Sep 2015. http://​www.​stemline.​com.
11.
12.
Angelot-Delettre F, Roggy A, Frankel AE, et al. In vivo and in vitro sensitivity of blastic plasmacytoid dendritic cell neoplasm to SL-401, an interleukin-3 receptor targeted biologic agent. Haematologica. 2015;100(2):223–30.CrossRefPubMedPubMedCentral
13.
Mani R, Goswami S, Gopalakrishnan B, et al. The interleukin-3 receptor CD123 targeted SL-401 mediates potent cytotoxic activity against CD34+ CD123+ cells from acute myeloid leukemia/myelodysplastic syndrome patients and healthy donors. Haematologica. 2018;103(8):1288–97.CrossRefPubMedPubMedCentral
14.
Ray A, Das DS, Song Y, et al. A novel agent SL-401 induces anti-myeloma activity by targeting plasmacytoid dendritic cells, osteoclastogenesis and cancer stem-like cells. Leukemia. 2017;31(12):2652–60.CrossRefPubMedPubMedCentral
15.
Kioon MD, Lindsay R, Chen J, et al. Sl-401, a novel targeted therapy directed to the interleukin-3 receptor (CD123), kills plasmacytoid dendritic cells from systemic sclerosis patients [abstract no. FRI0398]. Ann Rheum Dis. 2018;77(Suppl 2):731–2.
16.
Hogge DE, Feuring-Buske M, Gerhard B, et al. The efficacy of diphtheria-growth factor fusion proteins is enhanced by co-administration of cytosine arabinoside in an immunodeficient mouse model of human acute myeloid leukemia. Leuk Res. 2004;28(11):1221–6.CrossRefPubMed
17.
Kim HP, Frankel AE, Hogge DE. A diphtheria toxin interleukin-3 fusion protein synergizes with tyrosine kinase inhibitors in killing leukemic progenitors from BCR/ABL positive acute leukemia. Leuk Res. 2010;34(8):1035–42.CrossRefPubMed
18.
Gionco J, Chen J, Lindsay R, et al. SL-401, a targeted therapy directed to the interleukin-3 receptor (CD123), and SL-801, a reversible inhibitor of exportin-1 (XPO1), display synergistic anti-tumor activity against hematologic malignancies in vitro [abstract no. 4724]. Blood. 2016;128(22).
19.
Stephansky J, Togami K, Ghandi M, et al. Resistance to Sl-401 in AML and BPDCN is associated with loss of the diphthamide synthesis pathway enzyme DPH1 and is reversible by azacitidine [abstract no. 797]. Blood. 2017;130(Suppl 1).
20.
Pemmaraju N, Sweet KL, Lane AA, et al. Results of pivotal phase 2 trial of SL-401 in patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN) [abstract no. 1298]. Blood. 2017;130(Suppl 1).
21.
Sun W, Liu H, Kim Y, et al. First pediatric experience of SL-401, a CD123-targeted therapy, in patients with blastic plasmacytoid dendritic cell neoplasm: report of three cases. J Hematol Oncol. 2018;11(1):61.CrossRefPubMedPubMedCentral
22.
Lane AA, Sweet KL, Wang ES, et al. Results from ongoing phase 1/2 trial of SL-401 as consolidation therapy in patients with acute myeloid leukemia (AML) in remission with minimal residual disease (MRD) [abstract no. 2583]. Blood. 2017;130(Suppl 1).
23.
Frankel A, Liu J-S, Rizzieri D, et al. Phase I clinical study of diphtheria toxin-interleukin 3 fusion protein in patients with acute myeloid leukemia and myelodysplasia. Leuk Lymphoma. 2008;49(3):543–53.CrossRefPubMed
24.
Patnaik MM, Gupta V, Schiller GJ, et al. Results from ongoing phase 1/2 trial of SL-401 in patients with myeloproliferative neoplasms including chronic myelomonocytic leukemia and primary myelofibrosis [abstract no. 2908]. Blood. 2017;130(Suppl 1).
25.
Patnaik M, Ali H, Gupta V, et al. Results from ongoing phase 1/2 clinical trial of tagraxofusp (SL-401) in patients with relapsed/refractory chronic myelomonocytic leukemia (CMML) [abstract no. 1821]. Blood. 2018;132(Suppl 1).
26.
Pemmaraju N, Gupta V, Schiller G, et al. Results from ongoing phase 1/2 clinical trial of tagraxofusp (SL-401) in patients with intermediate or high risk relapsed/refractory myelofibrosis [abstract no. 1773]. Blood. 2018;132(Suppl 1).
Metadata
Title
Tagraxofusp: First Global Approval
Author
Yahiya Y. Syed
Publication date
01-04-2019
Publisher
Springer International Publishing
Published in
Drugs / Issue 5/2019
Print ISSN: 0012-6667
Electronic ISSN: 1179-1950
DOI
https://doi.org/10.1007/s40265-019-01087-z

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