PI-117

W. Y. Sohn,1 E. Lee,1 M. K. Kankam,2 O. Egbuna,1 G. Moffat,1 J. Bussiere,1 D. Padhi,1 E. W. Ng,1 S. Kumar,1 J. G. Slatter1; 1Amgen, Thousand Oaks, CA, 2Vince & Associates, Overland Park, KS

BACKGROUND: Denosumab (DMab) is a fully human monoclonal IgG2 antibody (mAb) that inhibits bone resorption. Physicochemical characteristics of mAbs limit passive transmission through biological membranes, and therefore are likely to limit distribution into semen, vaginal absorption, and maternal/fetal systemic exposure. This study addresses the potential for fetal exposure to DMAb in seminal fluid during unprotected sexual intercourse with a pregnant partner.
METHODS: An open-label, single-dose study in 12 healthy men was conducted over a 106-day period. Subjects received a single subcutaneous (SC) dose of 60 mg DMab on day 1. Serum and seminal fluid samples were collected to assess DMab pharmacokinetics and measured by a validated enzyme-linked immunosorbent assay (ELISA) (LLOQ: 20 ng/mL). Adverse events were recorded.
RESULTS: The mean (SD) Cmax was 6,170 (2,070) ng/mL (range: 3,300 - 9,030 ng/mL) in serum and 100 (81.9) ng/mL (range: 0 - 301 ng/mL) in seminal fluid. The median time to Cmax (tmax) in serum and seminal fluid was 8.0 days and 21 days, respectively. The mean (SD) area under the concentration-time curve from time zero to last quantifiable concentration (AUClast) was 333,000 (122,000) day•ng/mL for serum and 5,220 (4,880) day•ng/mL for seminal fluid. The mean (SD) Cmax and AUC ratios between seminal fluid and serum were 0.0217 (0.0154) and 0.0170 (0.0148), respectively. No new safety risks were identified.
CONCLUSIONS: DMab was measurable at low (~2%) concentrations in seminal fluid. Data were reviewed in context of preclinical safety data and conservative assumptions related to vaginal absorption from male partner and placental transfer to fetus of mAbs. These results indicate negligible risk to the fetus exposed to Dmab via seminal fluid transfer from male to pregnant partner.