Data
Animal Data
In a mouse embryo-fetal development study, a murine surrogate anti-mouse IFNγ antibody wasadministered every 3-4 days throughout organogenesis and late gestation at doses of 0, 30, 75 or150 mg/kg/occasion. The surrogate antibody was detected in the plasma of all treated pregnantmice and their corresponding fetuses. No maternal toxicity occurred and there was no evidenceof teratogenicity or effects on embryo-fetal survival or growth.
8.2 Lactation
Risk Summary
There is no information regarding the presence of emapalumab-lzsg in human milk, the effectson the breastfed child, or the effects on milk production. Published data suggest that only limitedamounts of therapeutic antibodies are found in breast milk and they do not enter the neonatal andinfant circulations in substantial amounts.
The developmental and health benefits of breastfeeding should be considered along with themother’s clinical need for GAMIFANT and any potential adverse effects on the breastfed childfrom GAMIFANT or from the underlying maternal condition.
8.4 Pediatric Use
Safety and effectiveness of GAMIFANT have been established in pediatric patients, newbornand older, with primary HLH that is reactivated or refractory to conventional therapies.
Use of GAMIFANT is supported by a single-arm trial in 27 pediatric patients with reactivated orrefractory primary HLH. This study included pediatric patients in the following age groups: 5patients newborn to 6 months, 10 patients 6 months to 2 years, and 12 patients from 2 years to 13years [see Clinical Studies (14)].
8.5 Geriatric Use
Clinical studies of GAMIFANT did not include sufficient numbers of subjects aged 65 and overto determine whether they respond differently from younger subjects. Other reported clinicalexperience has not identified differences in responses between the elderly and younger patients。
11 DESCRIPTION
Emapalumab-lzsg is an interferon gamma (IFNγ) blocking antibody. Emapalumab-lzsg is
produced in Chinese Hamster Ovary cells by recombinant DNA technology. Emapalumab-lzsg is
an IgG1 immunoglobulin with a molecular weight of approximately 148 kDa.
GAMIFANT (emapalumab-lzsg) injection for intravenous use is a sterile, preservative-free, clear
to slightly opalescent, colorless to slightly yellow solution provided in single-dose vials that
require dilution prior to intravenous infusion.
Each vial contains 10 mg/2 mL or 50 mg/10 mL emapalumab-lzsg at a concentration of 5
mg/mL. Each mL also contains the following inactive ingredients: L-Histidine (1.55 mg), LHistidine
monohydrochloride, monohydrate (3.14 mg), Polysorbate 80 (0.05 mg), sodium
chloride (7.30 mg), and Water for Injection, USP.
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
Emapalumab-lzsg is a monoclonal antibody that binds to and neutralizes interferon gamma(IFNγ). Nonclinical data suggest that IFNγ plays a pivotal role in the pathogenesis of HLH bybeing hypersecreted.
12.2 Pharmacodynamics
IFNγ Inhibition
Emapalumab-lzsg reduces the plasma concentrations of CXCL9, a chemokine induced by IFNγ.
Cardiac Electrophysiology
At a dose of 3 mg/kg GAMIFANT does not prolong the QT interval to any clinically relevantextent.
12.3 Pharmacokinetics
The pharmacokinetics of emapalumab-lzsg were eva luated in healthy adult subjects and inpatients with primary HLH.
Following |
