FDA Approves ELZONRIS (Tagraxofusp-erzs) Injection for Blastic Plasmacytoid Dendritic Cell Neoplasm in Adults and in Pediatric Patients 2 Years and Older

On December 21, 2018, the U.S Food and Drug Administration (FDA) approved ELZONRISTM (tagraxofusp-erzs) injection for the treatment of blastic plasmacytoid dendritic cell neoplasm (BPDCN) in adults and in pediatric patients 2 years and older. The approved recommended dosage of ELZONRIS is 12 mcg/kg as an intravenous infusion over 15 minutes once daily on days 1 to 5 of a 21-day cycle. The dosing period may be extended for dose delays up to day 10 of the cycle. Continue treatment with ELZONRIS until disease progression or unacceptable toxicity. Prior to the first dose of the first cycle, ensure serum albumin is ≥ 3.2 g/dL before administering ELZONRIS. Premedicate with an H1-histamine antagonist (e.g., diphenhydramine hydrochloride), H2-histamine antagonist (e.g., ranitidine), corticosteroid (e.g., 50 mg intravenous methylprednisolone or equivalent), and acetaminophen approximately 60 minutes prior to each ELZONRIS infusion.

Capillary leak syndrome (CLS), which may be life-threatening or fatal if not properly managed, can occur in patients receiving ELZONRIS. Additional information regarding warning and precautions including CLS, severe hypersensitivity reactions, and hepatotoxicity can be found in the full prescribing information linked below. 

Mechanism of Action (MOA) and General Pharmacokinetics (PK)

  • MOA: Tagraxofusp-erzs is a CD123-directed cytotoxin.
  • General PK: Following administration of the approved recommended dosage in patients with BPDCN, the mean (SD) tagraxofusp-erzs AUC was 231 (123) hr·mcg/L and Cmax was 162 (58.1) mcg/L.
  • Distribution: The mean volume of distribution is 5.1 (1.9) L.
  • Elimination: The mean terminal half-life is 0.7 (0.3) hours, and clearance is 7.1 (7.2) L/hr.
  • Immunogenicity: The presence of anti-drug antibodies (ADA) had a clinically significant effect on tagraxofusp-erzs PK. Titers of ADAs increased and free tagraxofusp-erzs concentration reduced in most plasma samples following doses given in Cycle 3. Following administration of the approved recommended dosage in patients with pre-existing ADAs, mean volume of distribution of tagraxofusp-erzs is 21.2 (25.4) L, clearance is 13.9 (19.4) L/hr, AUC is 151 (89.2) hr·mcg/L, and Cmax is 80.0 (82.2) mcg/L. 

Use in Specific Populations

No clinically significant differences in the PK of tagraxofusp-erzs were observed based on age (22 to 84 years), sex, mild to moderate renal impairment (eGFR 30 to 89 mL/min/1.73 m2, estimated by MDRD), mild (total bilirubin ≤ ULN and AST > ULN, or total bilirubin 1 to 1.5 times ULN and any AST) or moderate (total bilirubin > 1.5 to 3 times ULN and any AST) hepatic impairment, or body weight after adjusting dose by body weight. The effect of severe renal impairment (eGFR 15 to 29 mL/min/1.73 m2) or severe hepatic impairment (total bilirubin > 3 times ULN and any AST) on tagraxofusp-erzs PK is unknown.

Efficacy and Safety

Efficacy of ELZONRIS was demonstrated in a multicenter, open-label, single-arm, clinical trial which evaluated the effectiveness of ELZONRIS at the approved recommended dosage in patients with BPDCN. Additional information regarding the efficacy trial can be found in the full prescribing information linked below.

The most common adverse reactions (incidence ≥ 30%) were capillary leak syndrome, nausea, fatigue, peripheral edema, pyrexia, and weight increase.  Most common laboratory abnormalities (incidence ≥ 50%) are decreases in albumin, platelets, hemoglobin, calcium, and sodium, and increases in glucose, ALT, and AST.

Full prescribing information is available at https://go.usa.gov/xEazu.

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This communication was prepared by Office of Clinical Pharmacology, Office of Translational Sciences, CDER, FDA.