females to use acceptable contraceptive methods during ELZONRIS treatment and for at least 1 weekafter the last dose of ELZONRIS.
8.4 Pediatric Use
The safety and effectiveness of ELZONRIS for treatment of BPDCN have been established in pediatric patients2 years of age and older (no data for pediatric patients less than 2 years of age). Use of ELZONRIS in these agegroups 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 < 12years 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 forpediatric patients is extrapolated from the results of STML-401-0114 [see Clinical Studies 14.1, 14.2].
8.5 Geriatric Use
Of the 94 patients who received ELZONRIS at the labeled dose in STML-401-0114, 23% were 75 years andolder. The older patients experienced a higher incidence of altered mental status (including confusional state,delirium, mental status changes, dementia, and encephalopathy) than younger patients.
11 DESCRIPTION
Tagraxofusp-erzs, a CD123-directed cytotoxin, is a fusion protein comprised of a recombinant humaninterleukin-3 (IL-3) and truncated diphtheria toxin (DT). Tagraxofusp-erzs has an approximate molecularweight of 57,695 Daltons. Tagraxofusp-erzs is constructed by recombinant DNA technology and produced in
Escherichia coli cells.
ELZONRIS (tagraxofusp-erzs) injection is a preservative-free, sterile, clear, colorless solution that may containa few white to translucent particles and requires dilution prior to intravenous infusion.
ELZONRIS is supplied ata concentration of 1,000 mcg/mL in a single-dose vial. Each mL of ELZONRIS contains 1,000 mcgtagraxofusp-erzs, sodium chloride (4.38 mg), sorbitol (50 mg), tromethamine (2.42 mg) and Water for Injection,USP and pH is 7.5.
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
Tagraxofusp-erzs is a CD123-directed cytotoxin composed of recombinant human interleukin-3 (IL-3) andtruncated diphtheria toxin (DT) fusion protein that inhibits protein synthesis and causes cell death in CD123-expressing cells.
12.2 Pharmacokinetics
Following administration of tagraxofusp-erzs 12 mcg/kg via 15-minute infusion in patients with BPDCN, themean (SD) area under the plasma drug concentration over time curve (AUC) was 231 (123) hr·mcg/L andmaximum plasma concentration (Cmax) was 162 (58.1) mcg/L.
Distribution
Mean (SD) volume of distribution of tagraxofusp-erzs is 5.1 (1.9) L in patients with BPDCN.
Elimination
Mean (SD) clearance is 7.1 (7.2) L/hr in patients with BPDCN. Mean (SD) terminal half-life of tagraxofusperzsis 0.7 (0.3) hours.
Anti-Product Antibody Formation Affecting Pharmacokinetics
Pharmacokinetic data obtained following doses given in Cycle 3 showed increased titers of anti-drug antibodiesand reduced free ELZONRIS concentration in most plasma samples. Following administration of tagraxofusperzs12 mcg/kg via 15-minute infusion in patients with pre-existing anti-drug antibodies, the mean (SD) 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/Land Cmax is 80.0 (82.2) mcg/L.
Specific Populations
No clinically significant differences in the pharma |
