Follitropin alfa/Lutropin alfa(Follitropin alfa/Lutropin alfa) - 药物靶点：FSHR_在研适应症：促卵泡激素缺乏，促黄体激素缺乏_专利_临床

概要

基本信息

药物类型

激素

别名

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

+ [5]

靶点

FSHR

作用机制

FSHR激动剂(卵泡刺激素受体激动剂)

治疗领域

在研适应症

非在研适应症

原研机构

在研机构

非在研机构

最高研发阶段批准上市

首次获批日期

欧盟 (2007-06-25),

促卵泡激素缺乏促黄体激素缺乏

最高研发阶段(中国)-

特殊审评-

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序列信息

Sequence Code 3246α

当前序列信息引自: *****

Sequence Code 3253

当前序列信息引自: *****

Sequence Code 83626α

当前序列信息引自: *****

关联

16

项与 Follitropin alfa/Lutropin alfa 相关的临床试验

NCT04899193 / Completed临床1期

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.

开始日期2021-05-08

申办/合作机构

Merck Healthcare KGaA

NCT04719000 / Recruiting临床4期IIT

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.

开始日期2021-02-04

申办/合作机构

Merck & Co., Inc.

NCT04385342 / Unknown status临床4期IIT

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.

开始日期2020-06-30

申办/合作机构

Mansoura University

100 项与 Follitropin alfa/Lutropin alfa 相关的临床结果

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100 项与 Follitropin alfa/Lutropin alfa 相关的转化医学

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100 项与 Follitropin alfa/Lutropin alfa 相关的专利（医药）

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65

项与 Follitropin alfa/Lutropin alfa 相关的文献（医药）

2023-03-27·Diagnostics (Basel, Switzerland)

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

Article

作者: 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.

2021-10-01·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

作者: 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.

2021-05-17·Human reproduction (Oxford, England)1区 · 医学

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

1区 · 医学

Article

作者: Avril, C ; Lehert, P ; D’Hooghe, T ; Parinaud, J ; Wainer, R ; Rongières, C ; Porcu, G ; 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

1

项与 Follitropin alfa/Lutropin alfa 相关的新闻（医药）

2024-10-09

·默克Merck

默克辅助生殖药物倍果乐®（Pergoveris®）落地粤港澳大湾区

默克辅助生殖药物倍果乐®（Pergoveris®）于日前顺利获批引进粤港澳大湾区中山大学孙逸仙医院，内地患者可全球同步受益于这一全球首个且目前唯一符合FSH: LH（促卵泡素：促黄体素）2:1比例的r-hFSH/ r-hLH（重组人促卵泡素/重组人促黄体素）复方制剂。这是粤港澳大湾区执行“港澳药械通”后，首个获批在大湾区的医疗机构内进行临床使用的辅助生殖药物。全国生殖健康流行病学调查数据显示，2007-2020年间，我国不孕发病率已从12%升至18%，且仍有上升的趋势1。女性正常生育能力的维持，需要LH和FSH协同作用。LH和FSH的产生或作用受损（相对或绝对缺乏）会影响配子生成和性腺类固醇的产生，从而降低女性的生育能力。LH和FSH的缺乏是由于多种内外因素导致促性腺激素生成或作用减少所致。这些疾病通常表现为低E2和低/正常促性腺激素水平，在进行卵巢刺激时需要 FSH 和 LH 联合治疗优化卵巢反应2。多项临床数据显示，倍果乐®（Pergoveris®）相较于r-hFSH单药或尿源性hMG（人绝经期促性腺激素），可改善HH（低促性腺激素性性腺功能减退）人群、低/慢反应人群、低预后人群、因GnRH拮抗剂或激动剂而发生LH短暂性医源性缺乏人群及高龄人群的妊娠结局。3-9 默克中国医药健康辅助生殖事业部负责人吴劲表示：我们很高兴看到倍果乐®（Pergoveris®）落地粤港澳大湾区。孕育生命是默克的目标之一。患者的福祉就是我们努力的方向。怀揣‘成就夫妻，成为父母’的初心，我们将继续积极支持政府加快创新药物的引入，进一步提高药物可及性，帮助更多满怀希望的中国家庭孕育生机。倍果乐®（Pergoveris®）适用于严重缺乏LH和FSH的成年女性，以刺激卵泡发育。倍果乐®（Pergoveris®）在全球逾100个国家/地区获批，迄今已有约65,000新生儿在它的帮助下来到这个世界。参考文献 1.https://news.pku.edu.cn/jxky/c78bac82dc814bb9b095c90c44b56f45.htm 2. Kol. Clin Med Insights Reprod Health. 2014;8:59-64； 3. Carone et al. J Endocrinol Invest. 2012;35:996-1002; 4. Raju et al. Reprod Med Biol. 2012;11(3):129-133; 5. Mignini Renzini et al. J Assist Reprod Genet. 2017;34(12):1645-1651; 6. Chen MJ et al.. Front Endocrinol (Lausanne). 2022 Aug 15;13:931756.; 7. Bühler and Fischer. Gynecol Endocrinol. 2012;28(5):345-50; 8. Bielfeld AP, et al. Reprod Biomed Online. 2023 Nov 12;48(6)103725. ; 9. Fábregues et al. Gynecol Endocrinol. 2013;29(5):430-51. 向下滑动查看更多默克是一家全球领先的科技公司，专注于医药健康、生命科学和电子科技三大领域。全球大约63,000名员工服务于默克，通过创造更加愉悦和可持续性的生活方式，为数百万人的生活带来积极的影响。从先进的基因编辑技术和发现治疗具有挑战性疾病的独特方法，到实现设备的智能化——默克无处不在。2023年，默克在65个国家/地区的总销售额达210亿欧元。科学探索和负责任的企业精神一直是默克科技进步的关键，也是默克自1668年以来永葆活力的秘诀。默克家族作为公司的创始者至今仍持有默克大部分的股份，我们在全球都叫“默克”，仅美国和加拿大例外。默克的三大领域：医药健康、生命科学及电子科技在这两个国家分别称之为“EMD Serono”、“MilliporeSigma”和“EMD Electronics”。默克在中国已经有90年发展历史，目前拥有近4,500名员工，在北京、上海、无锡、苏州、南通、香港等地拥有21家注册公司。

上市批准临床结果

100 项与 Follitropin alfa/Lutropin alfa 相关的药物交易

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外链

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

研发状态

批准上市

10 条最早获批的记录,

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适应症	国家/地区	公司	日期
促卵泡激素缺乏	欧盟	Merck Europe BV	2007-06-25
促卵泡激素缺乏	冰岛	Merck Europe BV	2007-06-25
促卵泡激素缺乏	列支敦士登	Merck Europe BV	2007-06-25
促卵泡激素缺乏	挪威	Merck Europe BV	2007-06-25
促黄体激素缺乏	欧盟	Merck Europe BV	2007-06-25
促黄体激素缺乏	冰岛	Merck Europe BV	2007-06-25
促黄体激素缺乏	列支敦士登	Merck Europe BV	2007-06-25
促黄体激素缺乏	挪威	Merck Europe BV	2007-06-25

未上市

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
不孕	临床3期	德国	Merck KGaA	2014-01-31
无排卵	临床1期	德国	Merck KGaA	2015-01-31

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临床结果

适应症

分期

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT02047227 (ESPART, CTgov)	临床3期	不孕	939	rhLH+r-hCG+lutropin alfa+follitropin alfa+Pergoveris (Pergoveris)	膚壓廠衊網願願糧窪餘(廠繭衊鹹構獵蓋鹽廠鏇) = 鹹艱願窪膚廠蓋鹹鬱蓋繭構淵鹹築襯築糧觸蓋 (齋構鬱範選製鏇膚製網, 鹽簾鬱獵鏇餘簾膚網積 ~ 襯鏇齋憲簾膚襯積壓窪) 更多	-	2017-01-24
				GONAL-f (r-hFSH)+r-hCG+r-hFSH (GONAL-f)	膚壓廠衊網願願糧窪餘(廠繭衊鹹構獵蓋鹽廠鏇) = 襯鬱築選壓願鏇鬱遞膚繭構淵鹹築襯築糧觸蓋 (齋構鬱範選製鏇膚製網, 淵顧餘衊餘遞構齋餘餘 ~ 糧觸製願醖觸願醖醖膚) 更多
NCT02317809 (CTgov)	临床1期	无排卵	34	Liquid pergoveris (First Liquid Pergoveris, Then Freeze-dried Pergoveris)	餘獵糧選選選獵繭網製(蓋壓糧遞鹽膚艱餘願鹽) = 衊網獵築憲鹽蓋鹽繭遞醖觸構夢憲製膚築壓願 (鏇窪夢襯製襯夢簾構齋, 選淵構鹽繭壓範範選構 ~ 鹹鑰廠觸夢選構餘壓觸) 更多	-	2016-12-13
				Liquid pergoveris (First Freeze-dried Pergoveris, Then Liquid Pergoveris)	餘獵糧選選選獵繭網製(蓋壓糧遞鹽膚艱餘願鹽) = 衊醖繭遞襯夢窪廠蓋蓋醖觸構夢憲製膚築壓願 (鏇窪夢襯製襯夢簾構齋, 網鑰鏇鬱願蓋壓廠糧鑰 ~ 顧淵鹹鏇淵窪鬱鑰構選) 更多
NCT02244866 (Pubmed \| Hum Reprod) 人工标引	N/A	不孕	240	Recombinant follicle-stimulating hormone +recombinant luteinizing hormone	鏇壓鑰餘鏇蓋鏇鏇糧繭(鬱襯顧醖憲構淵構製築) = 窪鹹夢淵積窪積鏇蓋鑰遞簾願醖憲衊構範鏇窪 (構艱獵鹽積願範壓廠積 )	积极	2015-05-01
				Gonal-F	鏇壓鑰餘鏇蓋鏇鏇糧繭(鬱襯顧醖憲構淵構製築) = 製築築範網餘觸鹽簾鑰遞簾願醖憲衊構範鏇窪 (構艱獵鹽積願範壓廠積 )
NCT01297465 (PERSIST, CTgov)	临床3期	不孕	202	Recombinant human chorionic gonadotropin (r-hCG)+Gonal-f®+Pergoveris® (Gonal-f® Plus Pergoveris®)	鹽襯鑰繭鑰鏇遞遞膚淵(襯範廠簾醖觸簾構衊鹽) = 願鹹襯範鹽鬱窪蓋積鏇簾夢繭築鏇鬱齋糧廠壓 (鹽襯廠選範蓋鬱鹽鏇蓋, 繭壓願齋窪鑰壓憲築遞 ~ 糧膚淵繭鑰獵顧鬱夢襯) 更多	-	2014-02-24
				Recombinant human chorionic gonadotropin (r-hCG)+Pergoveris® (Pergoveris®)	鹽襯鑰繭鑰鏇遞遞膚淵(襯範廠簾醖觸簾構衊鹽) = 構築鬱鬱餘鹹繭糧築顧簾夢繭築鏇鬱齋糧廠壓 (鹽襯廠選範蓋鬱鹽鏇蓋, 艱範齋膚觸網鏇積齋醖 ~ 憲糧醖鑰製鏇廠夢積願) 更多