Elzonris Drug Information

is indicated for the treatment of blastic plasmacytoid dendritic cell neoplasm (BPDCN) in adults and in pediatric patients 2 years and older. ELZONRIS is a CD123-directed cytotoxin indicated for the treatment of blastic plasmacytoid dendritic cell neoplasm (BPDCN) in adults and in pediatric patients 2 years and older

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Safety of ELZONRIS was assessed in a single-arm clinical trial that included 122 adults with newly diagnosed or relapsed/refractory myeloid malignancies, including 86 with BPDCN, treated with ELZONRIS 12 mcg/kg daily for 5 days of a 21-day cycle. The overall median number of cycles started was 2.5 (range, 1-76), and 4 in patients with BPDCN (range, 1-76). Four (3%) patients (4/122) had fatal adverse reactions, all of which were related to capillary leak syndrome.

Overall, 8% (10/122) of patients discontinued treatment with ELZONRIS due to an adverse reaction; the most common adverse reactions resulting in treatment discontinuation were hepatic toxicities, hypoalbuminemia and CLS (2% each). Table 3 summarizes the common (≥ 10%) adverse reactions with ELZONRIS in patients with myeloid malignancies. The rate of any given adverse reaction or lab abnormality was derived from all the reported events of that type. Table 3. Adverse Reactions in ≥ 10% of Patients Receiving 12 mcg/kg of ELZONRIS 1 Capillary leak syndrome defined as any event reported as CLS during treatment with ELZONRIS or the occurrence of at least 2 of the following CLS manifestations within 7 days of each other: hypoalbuminemia (including albumin value less than 3.0 g/dL), edema (including weight increase of 5 kg or more), hypotension (including systolic blood pressure less than 90 mmHg). N=122 All Grades % Grade ≥ 3 % Vascular disorders Capillary leak syndrome 1 53 11 Hypotension 25 7 Hypertension 14 6 General disorders and administration site conditions Fatigue 45 7 Pyrexia 43 0 Peripheral edema 39 1 Chills 26 1 Gastrointestinal disorders Nausea 45 0 Constipation 24 0 Diarrhea 21 0 Vomiting 19 0 Investigations Weight increase 31 0 Nervous system disorders Headache 28 0 Dizziness 21 0 Metabolism and nutrition disorders Decreased appetite 22 0 Respiratory, thoracic and mediastinal disorders Dyspnea 20 3 Epistaxis 12 1 Cough 12 0 Blood and lymphatic system disorders Febrile neutropenia 19 16 Musculoskeletal and connective tissue disorders Back pain 19 2 Pain in extremity 10 2 Cardiac disorders Tachycardia 17 0 Psychiatric disorders Insomnia 16 0 Anxiety 15 0 Skin and subcutaneous tissue disorders Pruritus 10 0 Clinically relevant adverse reactions occurring in less than 10% of patients treated with ELZONRIS included tumor lysis syndrome.

Table 4 summarizes the clinically important laboratory abnormalities that occurred in ≥ 10% patients with myeloid malignancies treated with ELZONRIS. Table 4. Selected Laboratory Abnormalities in Patients Receiving 12 mcg/kg of ELZONRIS Treatment-Emergent Laboratory Abnormalities All Grades % Grade ≥ 3 % Hematology Platelets decrease 68 49 Hemoglobin decrease 61 30 Neutrophils decrease 38 29 Chemistry Glucose increase 89 21 ALT increase 79 26 AST increase 76 33 Albumin decrease 72 1 Calcium decrease 57 2 Sodium decrease 52 9 Potassium decrease 36 6 Phosphate decrease 32 10 Creatinine increase 26 0 Magnesium decrease 25 0 Alkaline phosphatase increase 22 1 Potassium increase 20 3 Magnesium increase 13 4 Bilirubin increase 11 0 Glucose decrease 10 0

Pregnancy Risk Summary Based on its mechanism of action, ELZONRIS has the potential for adverse effects on embryo-fetal development . There are no available data on ELZONRIS use in pregnant women to inform a drug-associated risk of adverse developmental outcomes. Animal reproduction or developmental toxicity studies have not been conducted with tagraxofusp-erzs. Advise pregnant women of the potential risk to the fetus.

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a risk of birth defect, loss, or other adverse outcomes. In the US general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4%, and 15% to 20%, respectively.

Pediatric Use The safety and effectiveness of ELZONRIS for treatment of BPDCN have been established in pediatric patients 2 years of age and older (no data for pediatric patients less than 2 years of age). Use of ELZONRIS in these age groups is supported by evidence from an adequate and well-controlled study of ELZONRIS in adults with BPDCN and additional safety data from three pediatric patients with BPDCN, including 1 child (2 years to < 12 years old) and 2 adolescents (12 years to < 17 years old), treated with ELZONRIS at the recommended dosage. The safety profile of ELZONRIS in the pediatric patients was similar to that seen in the adults. Efficacy for pediatric patients is extrapolated from the results of STML-401-0114. Safety and effectiveness have not been established in pediatric patients younger than 2 years of age.