Cough 12
Irritability 12
Tachycardia 12
Tachypnea 12
a
Includes viral, bacterial, fungal, and infections in which no pathogen was identified
b
Includes secondary hypertension
c
Includes events of drug eruption, pyrexia, rash, erythema, and hyperhidrosis Additional selected adverse reactions (all grades) that were reported in less than 10% of patientstreated with GAMIFANT included: vomiting, acute kidney injury, asthenia, bradycardia,dyspnea, gastro-intestinal hemorrhage, epistaxis, and peripheral edema.
6.2 Immunogenicity
As with all therapeutic proteins, there is potential for immunogenicity. The detection of antibodyformation is highly dependent on the sensitivity and specificity of the assay. Additionally, theobserved incidence of antibody (including neutralizing antibody) positivity in an assay may beinfluenced by several factors, including assay methodology, sample handling, timing of samplecollection, concomitant medications, and underlying disease. For these reasons, comparison ofthe incidence of antibodies in the studies described below with the incidence of antibodies inother studies or to other emapalumab products may be misleading.
The immunogenicity of emapalumab-lzsg has been eva luated using anelectrochemiluminescence-based immunoassay (ECLIA). A total of 64 subjects were eva luated
for anti-therapeutic antibodies (ATAs) to emapalumab-lzsg after treatment with GAMIFANT.
ATAs were detected in 3/64 subjects (5%) who received GAMIFANT.
Treatment-emergent ATAs were detected in 1/33 (3%) of patients in the primary HLH clinicaltrial. The ATAs in this patient were found to have neutralizing ability. One patient receivingGAMIFANT through compassionate use developed transient non-neutralizing treatmentemergentATAs. In both of these patients, ATAs occurred within the first 9 weeks following theinitiation of GAMIFANT treatment. In addition, one healthy subject tested positive for ATAsfollowing a single dose of GAMIFANT. No evidence of an altered safety or efficacy profile wasidentified in the primary HLH patients who developed antibodies to emapalumab-lzsg.
7 DRUG INTERACTIONS
7.1 Effect of GAMIFANT on Cytochrome P450 Substrates
The formation of CYP450 enzymes may be suppressed by increased levels of cytokines (such asIFNγ) during chronic inflammation. By neutralizing IFNγ, use of GAMIFANT may normalizeCYP450 activities which may reduce the efficacy of drugs that are CYP450 substrates due toincreased metabolism.
Upon initiation or discontinuation of concomitant GAMIFANT, monitor for reduced efficacyand adjust dosage of CYP450 substrate drugs as appropriate.
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
Risk Summary
There are no available data on GAMIFANT use in pregnant women to inform a drug-associatedrisk of adverse developmental outcomes. In an animal reproduction study, a murine surrogate anti-mouse IFNγ antibody administered to pregnant mice throughout gestation crossed theplacental barrier, and no fetal harm was observed (see Data).
The estimated background risk of major birth defects and miscarriage for the indicatedpopulation is unknown. All pregnancies have a background risk of birth defect, loss, or otheradverse outcomes. In the U.S. general population, the estimated background risk of major birthdefects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%,respectively. |
