A phase 3, double-blind, randomized, placebo-controlled study to assess the safety and efficacy of a single oral administration of nolasiban to increase ongoing pregnancy rate following fresh single blastocyst transfer resulting from IVF - IMPLANT 4

Start Date20 Mar 2019

Sponsor / Collaborator

ObsEva SA

NCT03758885 / CompletedPhase 3

A Phase 3, Double-blind, Randomized, Placebo-controlled Study to Assess the Safety and Efficacy of a Single Oral Administration of Nolasiban to Increase On-going Pregnancy Rate Following Fresh Single Blastocyst Transfer Resulting From IVF

The primary objective of this study is to confirm the efficacy of a single oral 900 mg dose of nolasiban versus placebo to increase the ongoing clinical pregnancy rate at 10 weeks post-embryo transfer (ET) day.

Start Date10 Jan 2019

Sponsor / Collaborator

ObsEva SA

EUCTR2016-004266-25-DE / Not yet recruitingPhase 3

A phase 3, double-blind, randomized, placebo-controlled study to assess the safety and efficacy of a single oral administration of nolasiban to improve pregnancy rates following IVF or ICSI in Day 3 and Day 5 fresh embryo transfer cycles

Start Date24 Apr 2017

Sponsor / Collaborator

ObsEva SA

100 Clinical Results associated with Erlosiban

100 Translational Medicine associated with Erlosiban

100 Patents (Medical) associated with Erlosiban

Literatures (Medical) associated with Erlosiban

01 Dec 2021·Reproductive BioMedicine OnlineQ3 · MEDICINE

Is oxytocin receptor antagonist administration around embryo transfer associated with IVF treatment success? A systematic review and meta-analysis

Q3 · MEDICINE

Review

Author: Griesinger, Georg ; Neumann, Kay

A systematic literature review and meta-analysis was conducted to evaluate whether the administration of an oxytocin receptor antagonist (OTR-a) around embryo transfer is associated with live birth and pregnancy achievement in IVF treatment. Multiple databases were searched for randomized controlled trials (RCT) comparing the outcome of IVF treatment with administration of an OTR-a before, during or after embryo transfer versus administration of placebo/nil. The literature search identified 11 eligible RCT. The active compound was intravenous atosiban (n = 7), subcutaneous barusiban (n = 1) and oral nolasiban (n = 3). Clinical pregnancy rate was significantly higher in women receiving an OTR-a around embryo transfer (relative risk [RR] 1.31, 95% confidence interval [CI] 1.13-1.51, P = 0.0002, I² = 61%, n = 11 studies, n = 3611); however, live birth rate was not statistically significantly affected (RR 1.09, 95% CI 0.98-1.20, P = 0.11, I² = 25%, n = 5 studies, n = 2765). 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, I² = 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.

01 Sep 2021·The Cochrane database of systematic reviews

Oxytocin antagonists for assisted reproduction.

Review

Author: Raine-Fenning, Nick ; Tsampras, Nikolaos ; Choudhary, Meenakshi ; Kollmann, Martina ; Craciunas, Laurentiu

BACKGROUNDEmbryo transfer (ET) is a crucial step of in vitro fertilisation (IVF) treatment, and involves placing the embryo(s) in the woman's uterus. There is a negative association between endometrial wave-like activity (contractile activities) at the time of ET and clinical pregnancy, but no specific treatment is currently used in clinical practice to counteract their effects. Oxytocin is a hormone produced by the hypothalamus and released by the posterior pituitary. Its main role involves generating uterine contractions during and after childbirth. Atosiban is the best known oxytocin antagonist (and is also a vasopressin antagonist), and it is commonly used to delay premature labour by halting uterine contractions. Other oxytocin antagonists include barusiban, nolasiban, epelsiban, and retosiban. Administration of oxytocin antagonists around the time of ET has been proposed as a means to reduce uterine contractions that may interfere with embryo implantation. The intervention involves administering the medication before, during, or after the ET (or a combination).OBJECTIVESTo evaluate the effectiveness and safety of oxytocin antagonists around the time of ET in women undergoing assisted reproduction.SEARCH METHODSWe searched the Cochrane Gynaecology and Fertility (CGF) Group trials register, CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL, and two trials registers in March 2021; and checked references and contacted study authors and experts in the field to identify additional studies.SELECTION CRITERIAWe included randomised controlled trials (RCTs) of the use of oxytocin antagonists for women undergoing ET, compared with the non-use of this intervention, the use of placebo, or the use of another similar drug.DATA COLLECTION AND ANALYSISWe used standard methodological procedures recommended by Cochrane. Primary review outcomes were live birth and miscarriage; secondary outcomes were clinical pregnancy and other adverse events.MAIN RESULTSWe included nine studies (including one comprising three separate trials, 3733 women analysed in total) investigating the role of three different oxytocin antagonists administered intravenously (atosiban), subcutaneously (barusiban), or orally (nolasiban). We found very low- to high-certainty evidence: the main limitations were serious risk of bias due to poor reporting of study methods, and serious or very serious imprecision. Intravenous atosiban versus normal saline or no intervention We are uncertain of the effect of intravenous atosiban on live birth rate (risk ratio (RR) 1.05, 95% confidence interval (CI) 0.88 to 1.24; 1 RCT, N = 800; low-certainty evidence). In a clinic with a live birth rate of 38% per cycle, the use of intravenous atosiban would be associated with a live birth rate ranging from 33.4% to 47.1%. We are uncertain whether intravenous atosiban influences miscarriage rate (RR 1.08, 95% CI 0.75 to 1.56; 5 RCTs, N = 1424; I² = 0%; very low-certainty evidence). In a clinic with a miscarriage rate of 7.2% per cycle, the use of intravenous atosiban would be associated with a miscarriage rate ranging from 5.4% to 11.2%. Intravenous atosiban may increase clinical pregnancy rate (RR 1.50, 95% CI 1.18 to 1.89; 7 RCTs, N = 1646; I² = 69%; low-certainty evidence), and we are uncertain whether multiple or ectopic pregnancy and other complication rates were influenced by the use of intravenous atosiban (very low-certainty evidence). Subcutaneous barusiban versus placebo One study investigated barusiban, but did not report on live birth or miscarriage. We are uncertain whether subcutaneous barusiban influences clinical pregnancy rate (RR 0.96, 95% CI 0.69 to 1.35; 1 RCT, N = 255; very low-certainty evidence). Trialists reported more mild to moderate injection site reactions with barusiban than with placebo, but there was no difference in severe reactions. They reported no serious drug reactions; and comparable neonatal outcome between groups. Oral nolasiban versus placebo Nolasiban does not increase live birth rate (RR 1.13, 95% CI 0.99 to 1.28; 3 RCTs, N = 1832; I² = 0%; high-certainty evidence). In a clinic with a live birth rate of 33% per cycle, the use of oral nolasiban would be associated with a live birth rate ranging from 32.7% to 42.2%. We are uncertain of the effect of oral nolasiban on miscarriage rate (RR 1.45, 95% CI 0.73 to 2.88; 3 RCTs, N = 1832; I² = 0%; low-certainty evidence). In a clinic with a miscarriage rate of 1.5% per cycle, the use of oral nolasiban would be associated with a miscarriage rate ranging from 1.1% to 4.3%. Oral nolasiban improves clinical pregnancy rate (RR 1.15, 95% CI 1.02 to 1.30; 3 RCTs, N = 1832; I² = 0%; high-certainty evidence), and probably does not increase multiple or ectopic pregnancy, or other complication rates (moderate-certainty evidence).AUTHORS' CONCLUSIONSWe 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.

01 Aug 2021·Reproductive BioMedicine OnlineQ3 · MEDICINE

The mechanism of action of oxytocin antagonist nolasiban in ART in healthy female volunteers

Q3 · MEDICINE

Article

Author: Marchand, Line ; Gotteland, Jean-Pierre ; Blockeel, Christophe ; Mackens, Shari ; Pohl, Oliver ; Lorch, Ulrike ; Pierzyński, Piotr

RESEARCH QUESTIONWhat are the effects of the oxytocin receptor (OTR) antagonist nolasiban on uterine contractions, endometrial perfusion and endometrial mRNA expression?DESIGNRandomized, double-blind, parallel-group, mechanism-of-action study with nolasiban. Forty-five healthy, pre-menopausal women were treated with placebo, 900 mg or 1800 mg nolasiban on the day corresponding to blastocyst transfer. Ultrasonographic uterine contraction frequency and endometrial perfusion were assessed, and endometrial biopsies analysed by next-generation sequencing.RESULTSBoth doses of nolasiban showed decreased contraction frequency and increased endometrial perfusion depending on the time point assessed. At 1800 mg, 10 endometrial genes (DPP4, CNTNAP3, CNTN4, CXCL12, TNXB, CTSE, OLFM4, KRT5, KRT6A, IDO2) were significantly differentially expressed (adjusted P < 0.05). Of these, OLFM4, DPP4 and CXCL12 were regulated in the same direction as genes involved in implantation during the window of implantation. In addition, three genes (DPP4, CXCL12 and IDO2) were associated with decidualization and endometrial receptivity.CONCLUSIONSThese 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.

News (Medical) associated with Erlosiban

08 Aug 2024

·www.biospace.com

Gameto Expands Executive Team with the Addition of Teri Loxam as Chief Financial Officer

NEW YORK, April 28, 2023 /PRNewswire/ -- Gameto, a female-led biotech company developing therapies to improve the female reproductive journey, today announced the expansion of its executive team with the appointment of Teri Loxam as its first Chief Financial Officer. In this new role, Teri will oversee Gameto's financial function, as well as play a key role in overall company strategy. "Teri is a proven CFO and an impressive female leader, whose decades of experience will immediately add value to our company," said Dina Radenkovic, co-founder and CEO of Gameto. "Her depth of knowledge in capital markets and financing in the biotechnology and pharmaceutical industries comes at an exciting time for the company as we work on clinical development and go-to-market strategy for our lead program, Fertilo, to make the IVF process shorter, safer and more effective for women. Teri's personal passion for women's health is extremely important to us as we continue to grow." Teri joins Gameto with over 20 years of diverse experience in strategy, investor relations and finance across the pharmaceutical, biotech, and TMT industries. Prior to joining Gameto, Teri was Chief Operating Officer & Chief Financial Officer at Kira Pharmaceuticals, a clinical-stage biotech company developing transformative therapies for people with complement-mediated diseases. There, she built financial and operational functions across the U.S. and China locations to get the company public-ready. Prior to Kira, Teri served as CFO of SQZ Biotechnologies, a novel cell therapy company developing treatments for cancer, infectious disease and other serious conditions, where she raised over $200M, including taking the company public in October 2020. Prior to joining SQZ, Teri held various positions at Merck, IMAX Corporation, and Bristol-Myers Squibb. Teri is also a member of the board of directors and audit chair of Vaxcyte, Inc. and Cardiol Therapeutics, Inc. She has a B.S. in Biology from the University of Victoria, B.C. Canada and an MBA from the University of California, Irvine. "Gameto's highly innovative platform and dedication to improve and support women's health is impressive," said Teri Loxam, Chief Financial Officer of Gameto. "I am eager to work with a talented team of professionals who are passionate about transforming the traditional IVF processes and advancing developments for women." Teri's appointment is one of many new senior hires this year. Gameto recently appointed Jean-Pierre Gotteland as Head of Development to the management team. Prior to joining Gameto, Jean-Pierre was Chief Scientific Officer and Head of R&D at ObsEva SA, a clinical-stage biotech company developing innovative women's reproductive health therapeutics. There, he led the development and approval of linzagolix, for uterine fibroids, and brought to clinical trials nolasiban, for increasing live birth rate following IVF. Jean-Pierre also served as Chief Development Officer at PregLem SA where he led the development and EU approval of ulipristal acetate for uterine fibroids and infertility. Prior to joining PregLem, Jean-Pierre held various R&D positions at Serono, a world-leading pharmaceutical company before its acquisition by Merck KgA. Jean-Pierre will facilitate clinical development of Gameto's lead program, Fertilo. These new senior hires expand the multidisciplinary team of stem cell engineers, computational biologists, embryologists and physicians Gameto has brought together. About Gameto Based in New York and Madrid, Gameto is a biotechnology company using cell engineering to develop therapeutics for diseases of the female reproductive system. Gameto brings together an experienced scientific management team with vision and passion to develop a product offering that will support women throughout their reproductive journey. Gameto is currently working on its first program, Fertilo, a product for IVF and egg freezing, aiming to make the process shorter, safer and more effective. The preclinical studies for Fertilo found that it can increase egg yield per cycle and maturation for both conventional and reduced stimulation cycle. Gameto is currently conducting preclinical studies with partners Inception Fertility, Spring Fertility, Extend Fertility, RMA, Pozitivf, Ovation Fertility, ReproART, Clinica Tambre, and Hospital Ruber Internacional, Eugin Group. Gameto is led by physician-turned-entrepreneur Dina Radenkovic as CEO and serial entrepreneur and leader in the fertility space Martin Varsavsky as Chairman. For more information, go to gametogen.com or follow us on Twitter and Instagram @gametogen.

Executive ChangeDrug Approval

28 Feb 2024

·www.fiercebiotech.com

ObsEva winds down and lays off all staff as money, options run out

Since being founded in 2012, ObsEva had racked up losses of $482.7 million. With its money and options dwindling, ObsEva has finally decided to wind down operations and lay off all its employees. The writing has been on the wall for the Swiss biotech since July 2022, when the company’s Nasdaq stock nosedived in the wake of the FDA’s claim that ObsEva’s highly touted uterine fibroid candidate linzagolix wasn’t fit for an on-time approval. In response, the company announced a 70% reduction in workforce two months later, with the remaining staff focused on preterm labor treatment ebopiprant and oral oxytocin receptor agonist nolasiban. By November 2022, the company had sold off ebopiprant to Xoma in an attempt to resuscitate its share price. When that failed, the company let go of its Boston-based executives—including CEO Brian O’Callaghan—and consolidated its remaining operations in Switzerland in February 2023. The company’s narrower focus became nolasiban, which it was investigating as a way to improve in vitro fertilization success rates. The company delisted from the Nasdaq the following month but has now informed the SIX Swiss Exchange's listing authority that it is “likely not going to be able to satisfy the requirements for maintaining its listing on SIX.” The Geneva-based company has secured a four-month moratorium from being chased by creditors for its debts until the end of May while it winds downs operations. Current CEO Fabien de Ladonchamps informed investors last month that ObsEva was “currently engaged in advanced negotiations for a transaction pertaining to nolasiban.” “While we are pursuing our efforts to monetize nolasiban, our compound designed to increase live birth rate for women undergoing IVF, ObsEva's cash position remains low, which compromises our ability to keep operating the company with existing workforce and to have financial statements prepared,” de Ladonchamps said in this morning's release. While de Ladonchamps' employment will be terminated along with all of his colleagues', ObsEva said he will “remain in function during the notice period for the duration of the moratorium process and beyond, as needed.” At its last earnings report back in the summer, ObsEva revealed that the $3.3 million it had available in cash and equivalents was likely to run out by the end of last year. Since being founded in 2012, the biotech had racked up losses of $482.7 million and “expects to continue to generate operating losses for the foreseeable future,” it said at the time.

Financial StatementExecutive ChangeClinical Trial Failure

28 Feb 2024

·www.biopharmadive.com

Women’s health company Obseva to wind down, lay off staff

Dive Brief:ObsEva, a womens health drug developer, on Wednesday said it plans to wind down its business and let go of all its employees.The company notified the Swiss stock exchange that it might not have the resources to put together its financial statements for 2023, nor maintain its listing. In January, the company was granted a moratorium during which its creditors are limited from making claims while it considers a restructuring or liquidation.ObsEva has been trying to negotiate a deal for its drug nolasiban, which is meant to help improve the chances of a successful pregnancy through in vitro fertilization. But the companys dwindling cash has weakened its ability to keep operating the company with existing workforce, CEO Fabien de Ladonchamps said in a statement.Dive Insight:ObsEvas planned wind-down follows several difficult years.In 2022, after negative feedback from the Food and Drug Administration and a delisting threat from the Nasdaq stock exchange, ObsEva said it would cut 70% of its workforce in an effort to stay afloat. Soon after, the companys chief scientific officer and head of R&D resigned.Not much later, ObsEva decided to drop another asset a drug for preterm birth by selling rights to Xoma Corp.Those moves didnt prevent further reorganization, however. Early this year, ObsEva announced it was consolidating its operations in Switzerland to preserve cash and focus on nolasiban. In March, ObsEva received another notice from the Nasdaq warning it would be delisted on March 23.ObsEva CEO Ladonchamps, who had previously worked at the company for nearly a decade, joined as CEO in May. Six months later, ObsEva sought court protection so it could focus on negotiating advantageous deals. '

Executive Change

100 Deals associated with Erlosiban

External Link

KEGG	Wiki	ATC	Drug Bank
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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Infertility	Phase 3	DE	ObsEva SA	06 Mar 2017
Infertility	Phase 3	HU	ObsEva SA	06 Mar 2017
Infertility	Phase 3	FI	ObsEva SA	06 Mar 2017
Infertility	Phase 3	BE	ObsEva SA	06 Mar 2017
Infertility	Phase 3	ES	ObsEva SA	06 Mar 2017
Infertility	Phase 3	EE	ObsEva SA	06 Mar 2017
Infertility	Phase 3	DK	ObsEva SA	06 Mar 2017
Infertility	Phase 3	PL	ObsEva SA	06 Mar 2017
Obstetric Labor, Premature	Phase 3	-	ObsEva SA	-
Obstetric Labor, Premature	Phase 3	-	Merck Serono SA	-

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02310802 \| NCT03081208 \| NCT03758885 (Pubmed \| Hum Reprod) Manual	Phase 2/3	Infertility, Female	1,710	nolasiban	mcaykgndam(zzgmrskycw) = a corresponding increase of 4.4% (95% CI -0.10, 8.93) in live birth rate compared to placebo xyeixvjmrh (gdiaytvhfi ) View more	Positive	18 Mar 2021
				placebo
NCT03758885 (IMPLANT4, GlobeNewswire) Manual	Phase 3	Infertility	807	Erlosiban	(ufknagqfpm) = owewplnszr oevqucbjjz (fttwudtbba )	Negative	07 Nov 2019
				Placebo	(ufknagqfpm) = vsukeladzd oevqucbjjz (fttwudtbba )
NCT03081208 (IMPLANT2, PipelineReview) Manual	Phase 3	Infertility	778	Nolasiban	(ewpwdkquqh) = tzngfjnspz tgrquirwar (trybcwceej ) View more	Positive	26 Feb 2018
				Placebo	(ewpwdkquqh) = wwjwypabht tgrquirwar (trybcwceej ) View more

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