Pregnancy & Breastfeeding
8.1 Pregnancy Risk Summary Available data with acoramidis use in pregnant women are insufficient to establish a drug associated risk of major birth defects, miscarriage or other adverse maternal or fetal outcomes. In animal reproductive studies in rats and rabbits, no embryofetal abnormalities were observed at exposures up to 34 times and 13 times the clinical exposure at the maximum recommended human dose, respectively ( see Data ). The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defects, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Report pregnancies to the BridgeBio reporting line at 1-844-550-2246. Data Animal Data In pregnant rats, oral administration of acoramidis (0, 50, 350, and 1,000 mg/kg/day) throughout organogenesis did not result in any adverse effects on embryofetal development at up to 1,000 mg/kg/day, approximately 34 times the clinical exposure at the maximum recommended human dose (MRHD) based on AUC. In pregnant rabbits, oral administration of acoramidis (0, 25, 75, and 200 mg/kg/day) throughout organogenesis resulted in increased pre-implantation loss at 200 mg/kg/day, a dose that caused maternal toxicity (26% reduced body weight gain). No embryofetal abnormalities were observed at 200 mg/kg/day, approximately 13 times the clinical exposure at the MRHD based on AUC. In a pre- and postnatal developmental toxicity study, pregnant rats received oral administration of acoramidis at doses of 0, 50, 350, or 1,000 mg/kg/day throughout pregnancy and lactation (Gestation Day 6 to Lactation Day 20). Maternal death, body weight reduction, and decreased number of females with live born pups (due to increase in resorbed litters) were observed at 1,000 mg/kg/day, approximately 43 times the clinica