Assessment of ixekizumab, an interleukin-17A monoclonal antibody, for potential effects on reproduction and development, including immune system function, in cynomolgus monkeys.
The reproductive and developmental toxicity of ixekizumab, a selective inhibitor of interleukin-17A (IL-17A), was assessed in the following studies in cynomolgus monkeys: fertility (3-month dosing), embryo-fetal development (EFD; dosing from gestation day (GD) 20 through 139), and pre-postnatal development (PPND; dosing from GD 20 through parturition). Because IL-17A has functional roles in innate and humoral immunity, immune system modulation was evaluated in the EFD and PPND studies; immunological evaluations in infants comprised peripheral blood immunophenotyping, Natural Killer cell cytolytic activity, and T-cell-dependent antibody (IgG and IgM) primary and secondary responses to antigen challenge. Ixekizumab exposure was sustained during the dosing periods in most adult monkeys. Fetal exposure at Cesarean section (GD 140-142; EFD study) was 18-25% of maternal exposure and ixekizumab was present in infants for up to 29 weeks postpartum. There were no adverse effects attributed to ixekizumab in any study. Importantly, immune system development and maturation were unaffected.
Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, IN 46285, United States. Electronic address: doclarke@lilly.com.
D O
DO
Clarke
Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, IN 46285, United States.
K G
KG
Hilbish
Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, IN 46285, United States.
D G
DG
Waters
Charles River Laboratories, 6995 Longley Lane, Reno, NV 89511, United States.
D L
DL
Newcomb
Charles River Laboratories, 6995 Longley Lane, Reno, NV 89511, United States.
G J
GJ
Chellman
D000367:Age Factors; D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000633:toxicity*; D015415:Biomarkers / Q000097:blood; D047108:Embryonic Development / Q000187:drug effects; D005260:Female; D005298:Fertility / Q000187:drug effects; D047109:Fetal Development / Q000187:drug effects; D005333:Fetus / Q000187:drug effects* / Q000276:immunology; D005865:Gestational Age; D007107:Immune System / Q000187:drug effects* / Q000196:embryology / Q000276:immunology; D007155:Immunologic Factors / Q000633:toxicity*; D008252:Macaca fascicularis; D008297:Male; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D012098:Reproduction / Q000187:drug effects*; D018570:Risk Assessment
D061067:Antibodies, Monoclonal, Humanized; D015415:Biomarkers; D007155:Immunologic Factors; C549079:ixekizumab
Cynomolgus monkey; Embryo-fetal; Fertility; Ixekizumab; Pre-postnatal; Toxicity