nolasiban (OBE001) / ObsEva, Hangzhou YuYuan Bioscience Technology - LARVOL DELTA

Relationships of Severity of Bronchopulmonary Dysplasia with Adverse Neurodevelopmental Outcomes and Poor respiratory Function at 7-8 Years of Age. (PubMed, J Pediatr) - "Compared with no BPD, receiving additional oxygen up to 29% but no positive pressure support at 36 weeks' postmenstrual age increased the risk of abnormal respiratory function but not adverse neurodevelopment. Receiving ≥30% oxygen or any positive pressure support at 36 weeks increased the risk of both adverse outcomes."

Journal • Bronchopulmonary Dysplasia • CNS Disorders • Developmental Disorders • Psychiatry • Pulmonary Disease • Respiratory Diseases

Novel Small Molecule Modulates Myometrial Cx43 and OXTR Expression Offering Effective Tocolysis. (SRI 2023) - "Ca2+ Assay: 1° CD31- myocytes (n=3) were exposed to candidate compound TK047 (20µM) for 4-hours and Ca2+ influx was measured using Calbryte (AAT Bioquest, Inc.) following OT-challenge (100nM) ± OXTR antagonist, nolasiban (600nM)... This novel class of small molecules decreases expression of OXTR and Cx43 in human uterine myocytes, while TK047 has further been shown to decrease Ca2+ influx and results in robust negative inotropic effects in whole myometrium, all but abolishing oxytocin-induced contractions. Taken together, these compounds represent a new and unique approach to tocolysis by targeting the expression and activity of multiple contractile proteins."

CD31 • GAPDH • PECAM1

Is oxytocin receptor antagonist administration around embryo transfer associated with IVF treatment success? A systematic review and meta-analysis. (PubMed, Reprod Biomed Online) - "The active compound was intravenous atosiban (n = 7), subcutaneous barusiban (n = 1) and oral nolasiban (n = 3)...A sensitivity analysis on low risk of bias studies likewise indicates a higher clinical pregnancy chance (RR 1.11, 95% CI 1.01-1.22, P = 0.03, I = 5%, n = 5 RCT, n = 2765). OTR-a administration in IVF treatment has the potential to increase IVF efficacy, although the treatment effects observed so far are small and have not been sufficiently corroborated."

Journal • Retrospective data • Review

IMPLANT4: Study of Nolasiban to Increase Pregnancy Rates in Women Undergoing IVF (clinicaltrials.gov) - P3; N=820; Completed; Sponsor: ObsEva SA; Active, not recruiting ➔ Completed

Clinical • Trial completion • Infertility • Sexual Disorders

Oxytocin antagonists for assisted reproduction. (PubMed, Cochrane Database Syst Rev) - "We are uncertain whether intravenous atosiban improves pregnancy outcomes for women undergoing assisted reproductive technology. This conclusion is based on currently available data from seven RCTs, which provided very low- to low-certainty evidence across studies. We could draw no clear conclusions about subcutaneous barusiban, based on limited data from one RCT. Further large well-designed RCTs reporting on live births and adverse clinical outcomes are still required to clarify the exact role of atosiban and barusiban before ET. Oral nolasiban appears to improve clinical pregnancy rate but not live birth rate, with an uncertain effect on miscarriage and adverse events. This conclusion is based on a phased study comprising three trials that provided low- to high-certainty evidence. Further large, well-designed RCTs, reporting on live births and adverse clinical outcomes, should focus on identifying the subgroups of women who are likely to benefit from this intervention."

Journal • Review • Gynecology

The mechanism of action of oxytocin antagonist nolasiban in ART in healthy female volunteers. (PubMed, Reprod Biomed Online) - "These data expand our knowledge of the mechanism of action of nolasiban in increasing pregnancy rates after embryo transfer. The results suggest more marked effects of nolasiban 1800 mg compared with the 900 mg dose, supporting testing at higher doses in IVF patients."

Clinical • IO biomarker • Journal • CXCL12 • DPP4 • KRT5

Confirmation of the cardiac safety of nolasiban in a randomised cohort of healthy female volunteers. (PubMed, Sci Rep) - "Heart rate was negatively correlated with progesterone. This study confirms the cardiovascular safety of nolasiban and describes relationships of sex hormones and ECG parameters."

Clinical • Journal • Cardiovascular

Effect of the oxytocin receptor antagonist nolasiban on pregnancy rates in women undergoing embryo transfer following IVF: analysis of three randomised clinical trials. (PubMed, Hum Reprod) - P2, P3 | "December 2014 (NCT02310802), March 2017 (NCT03081208), November 2018 (NCT03758885). January 2015 (NCT02310802), March 2017 (NCT03081208), November 2018 (NCT03758885)."

Clinical • Journal • Acute Respiratory Distress Syndrome • Critical care • Hepatology • Obstetrics • Respiratory Diseases

[VIRTUAL] THE USE OF NOLASIBAN, A NOVEL OXYTOCIN RECEPTOR ANTAGONIST, PRIOR TO EMBRYO TRANSFER: DOES IT HELP? (ISGE-I 2020) - "The meta-analysis suggests nolasiban may increase OPR. Further analyses will assess whether certain baseline factors may influence responses to nolasiban."

Gynecology

Oxytocin Receptor Antagonists, Atosiban and Nolasiban, Inhibit Prostaglandin F-induced Contractions and Inflammatory Responses in Human Myometrium. (PubMed, Sci Rep) - "We have demonstrated that atosiban and nolasiban not only inhibit contractions elicited by OT, but also inhibit contractions and inflammation induced by PGF. This suggests a possible crosstalk between OTR and PG receptor signalling and highlights the importance of understanding G protein-coupled receptor interactions/crosstalk in the development of future tocolytics."

Journal • Immunology • Inflammation

IMPLANT2: Phase 3 Placebo Controlled Study of Nolasiban to Improve Pregnancy Rates in Women Undergoing IVF/ICSI (clinicaltrials.gov) - P3; N=760; Active, not recruiting; Sponsor: ObsEva SA; Recruiting ➔ Active, not recruiting

Enrollment closed • Biosimilar • Long-acting Reversible Contraceptives • Women's Health

A Phase 2 Study of OBE001 Versus Placebo in the Delay of Preterm Birth (clinicaltrials.gov) - P2; N=100; Recruiting; Sponsor: ObsEva SA; Trial primary completion date: Sep 2015 ➔ Dec 2015

Trial primary completion date • Biosimilar

A Phase 2 Study of OBE001 Versus Placebo in the Delay of Preterm Birth (clinicaltrials.gov) - P2; N=100; Not yet recruiting; Sponsor: ObsEva SA

New P2 trial • Biosimilar

The use of a novel oxytocin receptor antagonist, nolasiban, prior to embryo transfer: does it help ? (ISGE 2020) - "The meta-analysis suggests nolasiban may increase OPR. Further analyses will assess whether certain baseline factors may influence responses to nolasiban."

IMPLANT2: Phase 3 Placebo Controlled Study of Nolasiban to Improve Pregnancy Rates in Women Undergoing IVF/ICSI (clinicaltrials.gov) - P3; N=810; Completed; Sponsor: ObsEva SA; Active, not recruiting ➔ Completed; Trial completion date: Nov 2019 ➔ Feb 2019

Clinical • Trial completion • Trial completion date

IMPLANT4: Study of Nolasiban to Increase Pregnancy Rates in Women Undergoing IVF (clinicaltrials.gov) - P3; N=820; Active, not recruiting; Sponsor: ObsEva SA; Recruiting ➔ Active, not recruiting

Clinical • Enrollment closed

IMPLANT2: Phase 3 Placebo Controlled Study of Nolasiban to Improve Pregnancy Rates in Women Undergoing IVF/ICSI (clinicaltrials.gov) - P3; N=760; Active, not recruiting; Sponsor: ObsEva SA; Trial completion date: Apr 2019 ➔ Nov 2019

Clinical • Trial completion date

IMPLANT4: Study of Nolasiban to Increase Pregnancy Rates in Women Undergoing IVF (clinicaltrials.gov) - P3; N=820; Recruiting; Sponsor: ObsEva SA; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open