ObsEva reports new clinical evidence of nolasiban MoA
ObsEva reported results from a mechanism of action, or MoA, trial of its oral oxytocin receptor antagonist, nolasiban. The trial assessed the effect of nolasiban on uterine contractions and endometrial blood flow, both of which are known to be associated with uterine receptivity and embryo implantation, and ultimately pregnancy and live birth following IVF. The effect of nolasiban administration on endometrial gene expression was also investigated. The randomized, double blind trial was conducted in 42 healthy female volunteers, aged 18 to 37 years, who had been pre-treated with a hormonal preparation identical to that used in women undergoing frozen-thawed embryo transfer. On the day corresponding to a Day 5 embryo transfer, subjects received a single, oral administration of the clinical dose of 900 mg nolasiban, a supra-therapeutic dose of 1800 mg nolasiban, or matching placebo. Pharmacodynamic, or PD, assessments up to 24 hours after treatment included measurements of uterine contraction frequency by ultrasound and uterine perfusion by 3D-power Doppler. Endometrial biopsy was obtained following PD assessments, and tissue samples analyzed for differential mRNA expression. "A single oral dose of nolasiban produced measurable and durable effects, with a reduction in the frequency of uterine contractions and a marked and sustained increase in endometrial blood flow. Within 24 hours of nolasiban administration, statistically significant changes were observed in the expression of a set of endometrial genes that have been described as potentially important in endometrial receptivity and embryonic implantation. These nolasiban trial results represent the first in vivo demonstration of the effect of oxytocin receptor inhibition on endometrial blood flow and receptivity-related gene expression. These important new MoA findings support the potential for nolasiban to increase live birth rates following IVF." The trial results are scheduled to be presented at an upcoming international OB/GYN conference.