normalities observed in ≥1% of the POTELIGEO arm included lymphopenia (5%), leukopenia(1%), and hypophosphatemia (1%).
6.2 Immunogenicity
As with all therapeutic proteins, there is a potential for immunogenicity. The detection of
antibody formation is highly dependent on the sensitivity and specificity of the assay.
Additionally, the observed incidence of antibody (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 underlying disease. For these reasons,
comparison of incidence of antibodies to POTELIGEO with the incidences of antibodies in other
studies or to other products may be misleading.
Among 258 patients treated with POTELIGEO in Trial 1, 10 (3.9%) tested positive for
treatment-emergent (treatment-induced or treatment-boosted) anti-mogamulizumab-kpkc
antibodies by an electrochemiluminescent assay. There were no positive neutralizing antibody
responses.
6.3 Postmarketing Safety Information
The following adverse reactions have been identified during post-approval use of POTELIGEO.
Because these reactions are reported voluntarily from a population of uncertain size, it is not
always possible to reliably estimate their frequency or establish a causal relationship to drug
exposure.
Infections: Hepatitis B virus reactivation
Cardiac disorders: Stress cardiomyopathy
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
Risk Summary
There are no available data on POTELIGEO use in pregnant women to inform a drug-associatedrisk of major birth defects and miscarriage. In an animal reproduction study, administration ofmogamulizumab-kpkc to pregnant cynomolgus monkeys from the start of organogenesis throughdelivery did not show a potential for adverse developmental outcomes at maternal systemicexposures 27 times the exposure in patients at the recommended dose, based on AUC (see Data).
In general, IgG molecules are known to cross the placental barrier and in the monkeyreproduction study mogamulizumab-kpkc was detected in fetal plasma. Therefore, POTELIGEO has the potential to be transmitted from the mother to the developing fetus. POTELIGEO is not recommended during pregnancy or in women of childbearing potential not using contraception.
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 risks of major birthdefects and miscarriage in clinically recognized pregnancies are 2-4% and 15-20%, respectively.
Data
Animal Data
The effects of mogamulizumab-kpkc on embryo-fetal development were eva luated in 12pregnant cynomolgus monkeys that received mogamulizumab-kpkc once weekly by intravenousadministration from the start of organogenesis through delivery at an exposure level 27 timeshigher than the clinical dose. Mogamulizumab-kpkc administration did not show a potential forembryo-fetal lethality, teratogenicity, or fetal growth retardation and did not result inspontaneous abortion or increased fetal death. In surviving fetuses (10 of 12 compared with 11 of12 in the control group) of cynomolgus monkeys treated with mogamulizumab-kpkc, a decrease
in CCR4-expressing lymphocytes due to the pharmacologi |
