The recent first global approval of tagraxofusp (Elzonris™) has been reviewed in detail in the First Global Approval report in Adis’ journal Drugs, based on the development milestones tracked in AdisInsight.
In December 2018, tagraxofusp, developed by Stemline Therapeutics, was approved by the United States Food and Drug Administration (FDA) for the treatment of blastic plasmacytoid dendritic cell neoplasm (BPDCN) in adults and children 2 years and older. Tagraxofusp is a CD123-directed cytotoxin composed of recombinant human interleukin-3 (IL-3) and truncated diphtheria toxin (DT) fusion protein. Administered intravenously, tagraxofusp ultimately results in cell death due to the inhibition of protein synthesis initiated by the drug binding to IL-3 receptors (CD123) overexpressed on certain haematological cancer cells.
Tagraxofusp was approved in the US based on the results of the STML-401-0114 study.
According to Andrew Lane, M.D., Ph.D., Assistant Professor at Harvard Medical School and Dana-Farber Cancer Institute and a principal investigator on the tagraxofusp clinical trial, “Tagraxofusp represents an unprecedented leap forward in the treatment of BPDCN, an aggressive malignancy with no approved therapeutic options until now.”
Tagraxofusp is the first drug to be approved for the treatment of BPDCN and represents the first approved CD123-targeted therapy. Tagraxofusp was granted priority review status, breakthrough therapy designation, and orphan drug designation by the FDA.
On the topic of the FDA approval of tagraxofusp, Naveen Pemmaraju, M.D., Associate Professor at The University of Texas MD Anderson Cancer Center and a principal investigator for the tagraxofusp clinical trial, stated, “[…] Approval of tagraxofusp is a major step forward for people with BPDCN, their families and the medical community.” This approval “represents a new standard of care for patients with BPDCN”, Pemmaraju explained.
Notably, the prescribing information for tagraxofusp carries a black box warning for capillary leak syndrome (CLS ). The prescribing information also warns of hypersensitivity and hepatotoxicity.
Tagraxofusp is also under review in the European Union for the same indication. Phase I and II investigations are being conducted in the US and Canada for the use of tagraxofusp in the treatment of chronic myelomonocytic leukemia (CMML), myelofibrosis, acute myeloid leukemia (AML), myelodysplastic syndromes, and multiple myeloma. Tagraxofusp is also in the preclinical development stage for certain autoimmune disorders.
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