Delving into the Latest Updates on Follitropin alfa/Lutropin alfa with Synapse

Overview

Basic Info

Drug Type

Hormone

Synonyms

Lutropin alfa/follitropin alfa, Pergoveris, Recombinant human follicle stimulating hormone/luteinising hormone

+ [5]

Target

FSHR

Mechanism

FSHR agonists(Follicle-stimulating hormone receptor agonists)

Therapeutic Areas

Nervous System DiseasesEndocrinology and Metabolic Disease

Active Indication

Follicle stimulating hormone deficiencyLuteinizing hormone deficiency

Inactive Indication

AnovulationInfertility

Originator Organization

Merck Serono SA

Active Organization

Merck Europe BV

Inactive Organization

Merck KGaA

Drug Highest PhaseApproved

First Approval Date

EU (25 Jun 2007),

Follicle stimulating hormone deficiencyLuteinizing hormone deficiency

Regulation-

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Structure/Sequence

Sequence Code 3246α

The sequence is quoted from: *****

Sequence Code 3253

The sequence is quoted from: *****

Sequence Code 83626α

The sequence is quoted from: *****

A Phase I, Open-label, Randomized, Three-period, Crossover, Single-center Trial to Assess the Bioequivalence of the Co-administration of 900 IU of Follitropin Alfa (Gonal-f) and 450 IU of Lutropin Alfa (Luveris) Versus the Fixed Combination of 900 IU Follitropin Alfa and 450 IU Lutropin Alfa in Pergoveris, Administered SC as Liquid and FD Formulation, in Pituitary Suppressed Healthy Premenopausal Female Chinese Participants

The main purpose of this study is to assess the bioequivalence (BE) of the fixed combination of follitropin alfa and lutropin alfa in Pergoveris freeze-dried (FD) (Test 1) or in Pergoveris Liquid (Test 2) versus the co-administration of Gonal-f and Luveris (Reference), administered subcutaneously (SC) in pituitary suppressed, healthy premenopausal Chinese female participants, at the doses of 900 international unit (IU) of follitropin alfa and 450 IU lutropin alfa.

Start Date08 May 2021

Sponsor / Collaborator

Merck Healthcare KGaA

NCT04719000

/ RecruitingPhase 4IIT

PErsonalized Addition of Recombinant LH in Suboptimal Responders >35 Years Old (POSEIDON Group 2): A Randomized Controlled Trial

Different ovarian stimulation regimens have shown to modify late follicular phase hormonal profiles. Besides, recent studies confirm that progesterone levels and their variation in the last day of oocyte maturation are affected by the dose of gonadotropins administered and by other factors. Progesterone elevation in late follicular phase of in vitro fertilization/intracytoplasmatic sperm injection (IVF/ICSI) cycles under ovarian stimulation compromises implantation rates due to a negative effect on the endometrium. However, there is still conflict in the literature questioning whether progesterone levels alone on the triggering day is a sufficient indicator as progesterone does not give the full picture of the ovarian functions, number of follicles as well as estrogen production that facilitate endometrial growth, thus some studies suggest that especially in aged and poor responders Progesterone/Estrogen (P4/E2) ratio has a better reflection (Progesterone (ng/mL) ×1,000/estradiol(pg/mL)) on the ovarian function.
The scope of the current pilot study is to compare serum progesterone levels as well as P4/E2 ratio on the day of ovulation triggering of women belonging to POSEIDON category group 2 who undergo a new ovarian stimulation with a dose of rhFSH 300 IU or 300 IU rhFSH plus 150 IU recombinant human luteinizing hormone (rhLH) in a gonadotropin-releasing hormone (GnRH) antagonist protocol.

Start Date04 Feb 2021

Sponsor / Collaborator

Merck & Co., Inc.

NCT04385342

/ Unknown statusPhase 4IIT

Follicle Stimulating Hormone (FSH) Followed by Human Menopausal Gonadotropin (HMG) Versus FSH Plus HMG During Controlled Ovarian Stimulation for in Vitro Fertilization

The aim of this study is to compare the clinical outcomes of sequential administration of FSH and HP-hMG FSH alone versus concomitant administration of FSH and HP-hMG during controlled ovarian stimulation in IVF cycles.

Start Date30 Jun 2020

Sponsor / Collaborator

Mansoura University

100 Clinical Results associated with Follitropin alfa/Lutropin alfa

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100 Translational Medicine associated with Follitropin alfa/Lutropin alfa

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100 Patents (Medical) associated with Follitropin alfa/Lutropin alfa

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65

Literatures (Medical) associated with Follitropin alfa/Lutropin alfa

27 Mar 2023·Diagnostics (Basel, Switzerland)

Corifolitropin-Alfa plus Five Days Letrozole Versus Daily Recombinant-FSH in Expected Normo-Responder Patients: A Retrospective Comparative Study.

Article

Author: D'Amato, Giuseppe ; Cicinelli, Ettore ; Cantatore, Clementina ; Vitagliano, Amerigo ; Stanziano, Antonio ; D'Amato, Antonio ; Caringella, Anna Maria

Background: In recent times, different novel GnRH-antagonist protocols with various combinations of gonadotropins and other molecules (e.g., aromatase inhibitors, selective estrogen receptor modulators) have been proposed for expected normal ovarian responders undergoing assisted reproductive treatments. The purpose of this study was to evaluate the effectiveness of a novel ovarian stimulation protocol based on the combination of corifollitropin-alfa plus five days of letrozole in E-NOR women undergoing IVF as compared with a daily recombinant-FSH regimen. Methods: We conducted a retrospective-controlled study on 182 couples undergoing their first IVF attempt. In Group A (experimental), letrozole (2.5 mg daily) was administered from day 2 (up to day 6 of the cycle), followed by corifollitropin-alfa on day 3 and daily recombinant FSH from day 10. In Group B, recombinant FSH from day 2 were administered (150 IU-225 IU daily). Statistical analysis was completed using SPSS Statistics. The primary outcome was the total number of MII oocytes retrieved. Results: Group A showed similar results compared to Group B in terms of MII oocytes, live birth, implantation, and clinical pregnancy rates (p = ns). Nevertheless, the experimental group was associated with a trend towards a higher number of developing follicles, total oocytes, and embryos (p < 0.05) with lower estradiol and progesterone values at ovulation induction compared to Group B, resulting in an increased chance of performing a fresh embryo transfer (p < 0.05). Conclusions: The combination of CFα plus five days of letrozole was associated with a trend towards a higher number of developing follicles, total oocytes, and obtained embryos. Moreover, the experimental protocol resulted in lower estradiol and progesterone values at ovulation induction compared to daily rFSH, with an increased chance of performing a fresh embryo transfer (with no OHSS occurrence). Given the observational design of our study, further well-conducted RCTs are needed.

01 Oct 2021·Revista brasileira de ginecologia e obstetricia : revista da Federacao Brasileira das Sociedades de Ginecologia e Obstetricia

Improving Implantation Rate in 2nd ICSI Cycle through Ovarian Stimulation with FSH and LH in GNRH Antagonist Regimen

Article

Author: Setti, Amanda Souza ; Borges, Edson ; Iaconelli, Assumpto ; Braga, Daniela Paes de Almeida Ferreira

Abstract:

Objective To investigate whether patients with a previous recombinant follicle stimulating hormone (rFSH)-stimulated cycle would have improved outcomes with rFSH + recombinant luteinizing hormone (rLH) stimulation in the following cycle. Methods For the present retrospective case-control study, 228 cycles performed in 114 patients undergoing intracytoplasmic sperm injection (ICSI) between 2015 and 2018 in an in vitro fertilization (IVF) center were evaluated. Controlled ovarian stimulation (COS) was achieved with rFSH (Gonal-f, Serono, Geneva, Switzerland) in the first ICSI cycle (rFSH group), and with rFSH and rLH (Pergoveris, Merck Serono S.p.A, Bari, Italy) in the second cycle (rFSH + rLH group). The ICSI outcomes were compared among the groups. Results Higher estradiol levels, oocyte yield, day-3 high-quality embryos rate and implantation rate, and a lower miscarriage rate were observed in the rFSH + rLH group compared with the rFSH group. In patients < 35 years old, the implantation rate was higher in the rFSH + rLH group compared with the rFSH group. In patients ≥ 35 years old, higher estradiol levels, oocyte yield, day-3 high-quality embryos rate, and implantation rate were observed in the rFSH + rLH group. In patients with ≤ 4 retrieved oocytes, oocyte yield, mature oocytes rate, normal cleavage speed, implantation rate, and miscarriage rate were improved in the rFSH + rLH group. In patients with ≥ 5 retrieved oocytes, higher estradiol levels, oocyte yield, and implantation rate were observed in the rFSH + rLH group. Conclusion Ovarian stimulation with luteinizing hormone (LH) supplementation results in higher implantation rates, independent of maternal age and response to COS when compared with previous cycles stimulated with rFSH only. Improvements were also observed for ICSI outcomes and miscarriage after stratification by age and retrieved oocytes.

17 May 2021·Human reproduction (Oxford, England)Q1 · MEDICINE

A large observational data study supporting the PROsPeR score classification in poor ovarian responders according to live birth outcome

Q1 · MEDICINE

Article

Author: Avril, C ; D’Hooghe, T ; Lehert, P ; Parinaud, J ; Wainer, R ; Porcu, G ; Rongières, C ; Massin, N ; Arvis, P ; Sagot, P

Abstract:

STUDY QUESTION:

Can the Poor Responder Outcome Prediction (PROsPeR) score identify live birth outcomes in subpopulations of patients with poor ovarian response (POR) defined according to the ESHRE Bologna criteria (female age, anti-Müllerian hormone (AMH), number of oocytes retrieved during the previous cycle (PNO) after treatment with originator recombinant human follitropin alfa?

SUMMARY ANSWER:

The PROsPeR score discriminated the probability of live birth in patients with POR using observational data with fair discrimination (AUC ≅ 70%) and calibration, and the AUC losing less than 5% precision compared with a model developed using the observational data.

WHAT IS KNOWN ALREADY:

Although scoring systems for the likelihood of live birth after ART have been developed, their accuracy may be insufficient, as they have generally been developed in the general population with infertility and were not validated for patients with POR. The PROsPeR score was developed using data from the follitropin alfa (GONAL-f; Merck KGaA, Darmstadt, Germany) arm of the Efficacy and Safety of Pergoveris in Assisted Reproductive Technology (ESPART) randomized controlled trial (RCT) and classifies women with POR as mild, moderate or severe, based upon three variables: female age, serum AMH level and number of oocytes retrieved during the previous cycle (PNO).

STUDY DESIGN, SIZE, DURATION:

The external validation of the PROsPeR score was completed using data derived from eight different centres in France. In addition, the follitropin alfa data from the ESPART RCT, originally used to develop the PROsPeR score, were used as reference cohort. The external validation of the PROsPeR score l was assessed using AUC. A predetermined non-inferiority limit of 0.10 compared with a reference sample and calibration (Hosmer–Lemeshow test) were the two conditions required for evaluation.

PARTICIPANTS/MATERIALS, SETTING, METHODS:

The observational cohort included data from 8085 ART treatment cycles performed with follitropin alfa in patients with POR defined according to the ESHRE Bologna criteria (17.6% of the initial data set). The ESPART cohort included 477 ART treatment cycles with ovarian stimulation performed with follitropin alfa in patients with POR.

MAIN RESULTS AND THE ROLE OF CHANCE:

The external validation of the PROsPeR score to identify subpopulations of women with POR with different live birth outcomes was shown in the observational cohort (AUC = 0.688; 95% CI: 0.662, 0.714) compared with the ESPART cohort (AUC = 0.695; 95% CI: 0.623, 0.767). The AUC difference was −0.0074 (95% CI: −0.083, 0.0689). This provided evidence, with 97.5% one-sided confidence, that there was a maximum estimated loss of 8.4% in discrimination between the observational cohort and the ESPART cohort, which was below the predetermined margin of 10%. The Hosmer–Lemeshow test did not reject the calibration when comparing observed and predicted data (Hosmer–Lemeshow test = 1.266688; P = 0.260).

LIMITATIONS, REASONS FOR CAUTION:

The study was based on secondary use of data that had not been collected specifically for the analysis reported here and the number of characteristics used to classify women with POR was limited to the available data. The data were from a limited number of ART centres in a single country, which may present a bias risk; however, baseline patient data were similar to other POR studies.

WIDER IMPLICATIONS OF THE FINDINGS:

This evaluation of the PROsPeR score using observational data supports the notion that the likelihood of live birth may be calculated with reasonable precision using three readily available pieces of data (female age, serum AMH and PNO). The PROsPeR score has potential to be used to discriminate expected probability of live birth according to the degree of POR (mild, moderate, severe) after treatment with follitropin alfa, enabling comparison of performance at one centre over time and the comparison between centres.

STUDY FUNDING/COMPETING INTEREST(S):

This analysis was funded by Merck KGaA, Darmstadt, Germany. P.L. received grants from Merck KGaA, outside of the submitted work. N.M. reports grants, personal fees and non-financial support from Merck KGaA outside the submitted work. T.D.H. is Vice President and Head of Global Medical Affairs Fertility, Research and Development at Merck KGaA, Darmstadt, Germany. P.A. has received personal fees from Merck KGaA, Darmstadt, Germany, outside the submitted work. C.R. has received grants and personal fees from Gedeon Richter and Merck Serono S.A.S., France, an affiliate of Merck KGaA, Darmstadt, Germany, outside the submitted work. P.S. reports congress support from Merck Serono S.A.S., France (an affiliate of Merck KGaA, Darmstadt, Germany), Gedeon Richter, TEVA and MDS outside the submitted work. C.A., J.P., G.P. and R.W. declare no conflict of interest.

TRIAL REGISTRATION NUMBER:

N/A

100 Deals associated with Follitropin alfa/Lutropin alfa

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External Link

KEGG	Wiki	ATC	Drug Bank
-	Follitropin alfa/Lutropin alfa	G03GA05	DB00094

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Follicle stimulating hormone deficiency	EU	Merck Europe BV	25 Jun 2007
Follicle stimulating hormone deficiency	IS	Merck Europe BV	25 Jun 2007
Follicle stimulating hormone deficiency	LI	Merck Europe BV	25 Jun 2007
Follicle stimulating hormone deficiency	NO	Merck Europe BV	25 Jun 2007
Luteinizing hormone deficiency	EU	Merck Europe BV	25 Jun 2007
Luteinizing hormone deficiency	IS	Merck Europe BV	25 Jun 2007
Luteinizing hormone deficiency	LI	Merck Europe BV	25 Jun 2007
Luteinizing hormone deficiency	NO	Merck Europe BV	25 Jun 2007

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Infertility	Phase 3	DE	Merck KGaA	31 Jan 2014
Anovulation	Phase 1	DE	Merck KGaA	31 Jan 2015

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02047227 (ESPART, CTgov)	Phase 3	Infertility	939	rhLH+r-hCG+lutropin alfa+follitropin alfa+Pergoveris (Pergoveris)	tfnlfbykbq(uyobbqrqju) = hbitfulgme yujuyoqhep (eawdxsyuhs, pjnnvddfly - ypsuyyusvy) View more	-	24 Jan 2017
				GONAL-f (r-hFSH)+r-hCG+r-hFSH (GONAL-f)	tfnlfbykbq(uyobbqrqju) = kzfnvrtiae yujuyoqhep (eawdxsyuhs, dbekvrrcwq - zpuxgomjww) View more
NCT02317809 (CTgov)	Phase 1	Anovulation	34	Liquid pergoveris (First Liquid Pergoveris, Then Freeze-dried Pergoveris)	fqttssfpoj(hhkgcycikt) = rgurdetkri ziiyyauoda (wxdnmmsylz, qavqdzqtdn - jwpkihfksk) View more	-	13 Dec 2016
				Liquid pergoveris (First Freeze-dried Pergoveris, Then Liquid Pergoveris)	fqttssfpoj(hhkgcycikt) = nyagahvoie ziiyyauoda (wxdnmmsylz, wbhuebsudb - srxarzlmag) View more
NCT02244866 (Pubmed \| Hum Reprod) Manual	Not Applicable	Infertility	240	Recombinant follicle-stimulating hormone +recombinant luteinizing hormone	cxfzhxpxpg(kgpfcwkyux) = fduleibype fpuzzaxkmi (xfcsjtoiyd )	Positive	01 May 2015
				Gonal-F	cxfzhxpxpg(kgpfcwkyux) = isfxwtwowx fpuzzaxkmi (xfcsjtoiyd )
NCT01297465 (PERSIST, CTgov)	Phase 3	Infertility	202	Recombinant human chorionic gonadotropin (r-hCG)+Gonal-f®+Pergoveris® (Gonal-f® Plus Pergoveris®)	fmvujlbyip(qhlrsgdhlc) = ndyptblhoy tiqkamkumg (jsrpmavcou, ldqayspkaj - jvduylhprx) View more	-	24 Feb 2014
				Recombinant human chorionic gonadotropin (r-hCG)+Pergoveris® (Pergoveris®)	fmvujlbyip(qhlrsgdhlc) = gqrqlpuime tiqkamkumg (jsrpmavcou, rzkqcrtnng - rmabucxkpo) View more