dy (including neutralizing antibody) positivity in an assay may be influenced by several factors including
assay methodology, sample handling, timing of sample collection, concomitant medications, and underlyingdisease. For these reasons, comparison of the incidence of antibodies to ELZONRIS with the incidences ofantibodies to other products may be misleading.
Immune response to ELZONRIS was eva luated by assessment of serum binding reactivity against ELZONRIS(anti-drug antibodies; ADA) and neutralizing antibodies by inhibition of functional activity. Immune responseto ELZONRIS was assessed using two immunoassays.
The first assay detected reactivity directed againstELZONRIS (ADA), and the second assay detected reactivity against the interleukin-3 (IL-3) portion ofELZONRIS. Two cell-based assays were used to investigate the presence of neutralizing antibodies byinhibition of a cell-based functional activity.
The presence of ADA had a clinically significant effect on the pharmacokinetics of tagraxofusp-erzs [see
Clinical Pharmacology (12.3)]. In 130 patients treated with ELZONRIS in 4 clinical trials:
• 96% (115/120) of patients eva luable for the presence of pre-existing ADA at baseline before treatment
were confirmed positive with 21% being positive for the presence of neutralizing antibodies. The high
preva lence of ADA at baseline was anticipated due to diphtheria immunization.
• 99% (107/108) of patients eva luable for treatment-emergent ADA tested positive with most patients
showing an increase in ADA titer by the end of Cycle 2 of ELZONRIS.
• 85% (86/101) of ADA-positive patients eva luable for the presence of neutralizing antibodies were
neutralizing antibody-positive.
• 68% (73/108) of patients eva luable for treatment-emergent anti-IL-3 antibodies tested positive with most
patients testing positive by Cycle 3 of ELZONRIS.
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
Risk Summary
Based on its mechanism of action, ELZONRIS has the potential for adverse effects on embryo-fetaldevelopment [see Clinical Pharmacology (12.1)]. There are no available data on ELZONRIS use in pregnantwomen to inform a drug-associated risk of adverse developmental outcomes. Animal reproduction ordevelopmental toxicity studies have not been conducted with tagraxofusp-erzs. Advise pregnant women of thepotential 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, theestimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to4%, and 15% to 20%, respectively.
8.2 Lactation
Risk Summary
No data are available regarding the presence of ELZONRIS in human milk, the effects on the breastfed child, orthe effects on milk production. Because of the potential for serious adverse reactions in breastfed children fromELZONRIS, breast feeding is not recommended during treatment and for 1 week after the last dose.
8.3 Females and Males of Reproductive PotentialBased on its mechanism of action, ELZONRIS may cause fetal harm when administered to a pregnant woman[see Use in Specific Populations (8.1)].
Pregnancy Testing:
Conduct pregnancy testing in females of reproductive potential within 7 days prior to initiating ELZONRIStreatment.
Contraception:
Advise |
