Advertisement

Drugs

, Volume 79, Issue 5, pp 579–583 | Cite as

Tagraxofusp: First Global Approval

  • Yahiya Y. SyedEmail author
AdisInsight Report
  • 144 Downloads

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.

Notes

Compliance with Ethical Standards

Funding

The preparation of this review was not supported by any external funding.

Conflict of interest

During the peer review process the manufacturer of the agent under review was offered an opportunity to comment on the article. Changes resulting from any comments received were made by the authors on the basis of scientific completeness and accuracy. Yahiya Y. Syed is a salaried employee of Adis/Springer, is responsible for the article content and declares no relevant conflicts of interest.

References

  1. 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.CrossRefGoogle Scholar
  2. 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.CrossRefGoogle Scholar
  3. 3.
    Pemmaraju N. Blastic plasmacytoid dendritic cell neoplasm. Clin Adv Hematol Oncol. 2016;14(4):220–3.Google Scholar
  4. 4.
    Stemline Therapeutics. Elzonris (tagraxofusp-erzs): US prescribing information. 2018. https://www.fda.gov/. Accessed 29 Jan 2019.
  5. 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. 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. 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. 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. 9.
    Stemline Therapeutics. Stemline Therapeutics announces SL-401 receives EU orphan drug designation for treatment of BPDCN [media release]. 2 Nov 2015. http://www.stemline.com.
  10. 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. 11.
    Stemline Therapeutics. Stemline Therapeutics in-licenses phase I oncology compound [media release]. 7 Mar 2007. http://www.stemline.com.
  12. 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.CrossRefGoogle Scholar
  13. 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.CrossRefGoogle Scholar
  14. 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.CrossRefGoogle Scholar
  15. 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.Google Scholar
  16. 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.CrossRefGoogle Scholar
  17. 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.CrossRefGoogle Scholar
  18. 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).Google Scholar
  19. 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).Google Scholar
  20. 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).Google Scholar
  21. 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.CrossRefGoogle Scholar
  22. 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).Google Scholar
  23. 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.CrossRefGoogle Scholar
  24. 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).Google Scholar
  25. 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).Google Scholar
  26. 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).Google Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.SpringerAucklandNew Zealand

Personalised recommendations