Pregnancy & Breastfeeding
8.1 Pregnancy Risk Summary There are no available data on EKTERLY in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage or other adverse maternal or fetal outcomes. In animal reproduction studies, oral administration of sebetralstat to pregnant rats and rabbits during organogenesis produced no evidence of fetal harm with dose exposures up to approximately 15 and 11 times, respectively, the human exposure at the maximum recommended human dose (MRHD) of up to 1,200 mg (on an area under the curve [AUC] basis). Sebetralstat produced an increase in embryofetal losses and fetal malformations in rats at an exposure that was 60 times the MRHD (see Data) . The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriages in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Animal Data In an embryofetal development study with pregnant rats dosed by the oral route during the period of organogenesis from gestation days 6 to 17, sebetralstat caused a dose-related increase in the incidence of external and visceral malformations, described as cleft palates and ventricular septal defects and an increase in embryofetal losses (early and late fetal deaths, mean number of live fetuses, and post-implantation loss at an exposure that was 60 times the MRHD (on an AUC basis with a maternal dose of 600 mg/kg/day)). Maternal toxicity, as evidenced by decreased body weight gains, was observed at exposures 60 times the MRHD (on an AUC basis with a maternal oral dose of 600 mg/kg/day). No fetal or maternal toxicities were observed at exposures up to 15 times the MRHD (on an AUC basis with a maternal oral dose of 300 mg/kg/day). In an embryofetal development study with pregnant rabbits dosed by