Results demonstrate a statistically significant improvement in ongoing pregnancy benefit at 10 weeks following a single, oral dose of nolasiban.
Herman Tournaye, MD, PhD
ObsEva SA reported topline positive results from the IMPLANT2 phase 3 clinical trial of its oral oxytocin receptor antagonist, nolasiban, a treatment being developed for improving pregnancy rate following in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) procedures.
IMPLANT2, the randomized clinical trial, included 778 patients from 41 fertility clinics across 8 European countries. Following ovarian stimulation, egg retrieval and fertilization, eligible women were randomized to receive either a single 900 mg dose of nolasiban or a placebo, 4 hours before day 3 or day 5 of a fresh, single embryo transfer.
Participant recruitment included patients undergoing single, fresh embryo transfer on day 3 (D3, n=388) or on day 5 (D5, n=390) after oocyte retrieval.
The primary endpoint of the trial included ongoing pregnancy demonstrated by ultrasound at 10 weeks following embryo transfer. Women with confirmed pregnancies are monitored until delivery with the infants observed for up to 6 months following birth.
"Given the emotional and financial costs of both IVF failures as well as multiple births, we believe that phase 3 IMPLANT2 results for nolasiban could represent a future paradigm shift in the field of IVF," Ernest Loumaye, MD, PhD, OB/GYN, chief executive officer and co-founder, ObsEva told MD Magazine. "As a potential first in class product we expect significant interest in findings — an 11% absolute and 32% relative improvement in 10-week pregnancy rates with nolasiban administration 5 days post the transfer of a single embryo."
The topline results include efficacy and safety data up to week 10 of pregnancy following embryo transfer. The primary endpoint was met, with an absolute increase in ongoing pregnancy rate at 10 weeks of 7.1% (placebo 28.5% and nolasiban 35.6%).
The increase of the ongoing pregnancy rate represents a relative increase of 25% in the rate after administration of nolasiban versus placebo.
In the embryo transfer D3 subgroup, there was a statistically non-significant 3.1% absolute increase in favor of nolasiban or a 14% relative increase in ongoing pregnancy rate after administration of nolasiban versus placebo.
Overall, nolasiban was well tolerated with a low rate of treatment discontinuation comparable to placebo. The safety profile was also similar to placebo with a total of 9 (2.3%) serious adverse effects in the placebo group and 4 (1%) in the nolasiban group.
“As the global IVF standard of care moves to day 5 embryo transfer, the IMPLANT2 results are highly relevant in that an approximate 30% increase in ongoing clinical pregnancy would constitute a major step forward in the field,” principal investigator, Herman Tournaye, MD, PhD, head of the Centre for Reproductive Medicine, University Hospital Brussels, said in a statement.
Nolasiban, an oral oxytocin receptor antagonist, has the potential to decrease uterine contractions, improve blood flow and enhance the receptivity of the endometrium to embryo implantation — all of which can increase the chance of a successful pregnancy and live-birth among women undergoing assisted reproduction technology.
"Any “add-on” treatment that can give a bonus of >5% extra chance to have an ongoing pregnancy is more than welcome in our domain," Tournaye told MD Magazine. "Moreover, if this "add-on” consist of an oral single dose, this is an extra bonus."
Expected to be reported in the fourth quarter of 2018, follow-up data from the study will include live birth rate and 28-day neonatal safety, while 6-month infant follow-up is expected to be available in 2019.
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