Key result
Oral letermovir achieves therapeutic maternal and fetal levels, supporting its use for congenital CMV.
Why the study?
No validated prenatal treatment exists for fetuses infected with congenital cytomegalovirus despite its prevalence and severe outcomes.
Does oral letermovir achieve therapeutic fetal exposure in pregnant women?
Does oral letermovir achieve therapeutic fetal exposure in pregnant women?
Letermovir achieves therapeutic fetal concentrations when administered to pregnant women, providing a pharmacological rationale for its use in congenital CMV therapy.
Premature for congenital CMV use; leaves open whether letermovir achieves therapeutic fetal brain exposure.
BACKGROUND: Cytomegalovirus (CMV) affects 0.5%-2.0% of all live births and is the main nongenetic cause of congenital sensorineural hearing loss and neurological damage, yet no validated prenatal treatment exists for infected fetuses. Letermovir, a CMV-specific antiviral, is approved for prophylaxis in transplant recipients. This study aimed to quantify maternal-fetal exposure to letermovir following maternal administration, focusing on CMV-target fetal organs, particularly the brain. METHODS: Seven pregnant women undergoing second-trimester termination of pregnancy for fetal anomalies received oral letermovir (240 or 480 mg once daily) for 3 days. On the day of termination, samples from maternal and fetal blood, placenta, and fetal organs were collected and analyzed. Plasma and tissue drug concentrations were compared to the letermovir half-maximal effective concentration to assess potential antiviral efficacy. RESULTS: Letermovir achieved therapeutic levels in all compartments. Complementary physiologically based pharmacokinetic modeling confirmed adequate fetal exposure across pregnancy stages. No maternal adverse events were observed. CONCLUSIONS: These unique in vivo data provide the first pharmacological rationale supporting letermovir use during pregnancy for congenital CMV therapy. Clinical Trials Registration. NCT04732260.
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Faure‐Bardon et al. (2025) studied Congenital Cytomegalovirus (CMV) risk (n=7). Letermovir was evaluated on Maternal-fetal exposure to letermovir (plasma and tissue drug concentrations). Oral letermovir (240 or 480 mg) administered to 7 pregnant women for 3 days achieved therapeutic levels in all maternal and fetal compartments, supporting its use for congenital CMV therapy.
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