SAINT-PREX, Switzerland--(BUSINESS WIRE)--Ferring Pharmaceuticals announced today that Swissmedic has approved Rekovelle® (follitropin delta) for use in controlled stimulation for induction of the development of multiple follicles in women undergoing assisted reproductive technologies (ART), such as an in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI).1 Rekovelle is a new human recombinant follicle stimulating hormone (human rFSH) and the first to use an approved individualised dosing regimen, based on a woman’s anti-Müllerian hormone (AMH) level and body weight.1,2
“With Ferring’s headquarters in Switzerland, we are particularly proud to announce the Swissmedic approval of Rekovelle, the first fertility medication to offer women a personalised approach, right from the start of treatment,” said Michel Pettigrew, President of the Executive Board and Chief Operating Officer, Ferring Pharmaceuticals. “The addition of Rekovelle to Ferring’s reproductive health portfolio reflects our ongoing commitment to addressing unmet patient needs at each stage of the fertility journey, from conception to birth.”
The Swissmedic approval was based on data from a comprehensive clinical development programme, including the Phase 3 ESTHER trials (Evidence-based Stimulation Trial with Human recombinant FSH in Europe and Rest of World), involving patients in 11 countries and over 2,000 cycles of controlled stimulation, also known as controlled ovarian stimulation (COS).2,3 The data showed that women receiving individualised treatment with Rekovelle, compared to conventional dosing with follitropin alfa*, had similar ongoing pregnancy and embryo implantation rates. Secondary endpoints† showed that 43% of women treated with Rekovelle achieved the target ovarian response of 8–14 oocytes (eggs), compared to 38% of women treated with follitropin alfa. Rekovelle’s individualised dosing regimen aims to obtain an ovarian response associated with a favourable safety/efficacy profile, i.e. aims to achieve an adequate number of eggs and reduce interventions to prevent ovarian hyperstimulation syndrome (OHSS). This dosing regimen is specific to Rekovelle and cannot be applied to other fertility treatments.
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About Rekovelle (follitropin delta)
Rekovelle is the first recombinant follicle stimulating hormone (rFSH) derived from a human cell line (PER.C6® cell line). Rekovelle is structurally and biochemically distinct from other existing rFSH treatments.1,4 The individualised dosing of Rekovelle is determined using an approved algorithm, based on a woman’s anti-Müllerian hormone (AMH) level and body weight.1,2,5 AMH will be measured by a companion diagnostic, the Elecsys® AMH Plus immunoassay from F. Hoffmann-La Roche Ltd (Roche).6,7
Rekovelle is currently approved in 34 countries and is available in 11 countries worldwide.
About controlled ovarian stimulation
Controlled stimulation, or controlled ovarian stimulation (COS), is the process by which a pharmacological treatment is used to induce the development of multiple ovarian follicles to obtain multiple eggs at follicular aspiration (egg retrieval from the ovaries). COS is required prior to assisted reproductive technologies (ART) such as in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI).8
About anti-Müllerian hormone (AMH) and ovarian hyperstimulation
AMH is a biomarker used to assess ovarian reserve and can help predict ovarian response.9 Women with high AMH levels are at an increased risk of developing OHSS, a potential complication of IVF treatment.10,11 Symptoms of early OHSS may include abdominal distension or discomfort, nausea and vomiting. In more severe cases OHSS can lead to large amounts of ascites (fluid accumulation in the abdominal cavity), shortness of breath, blood clots, dehydration and potentially, death.10
The prevalence of OHSS in women undergoing IVF varies according to severity, with cases of OHSS experienced by 20–33% (mild), 3–6% (moderate) and 0.1–2% (severe) of women.12 A recent report suggested that OHSS is an underreported side effect of COS and the real world incidence may be higher.13 In addition to the impact on patients, the treatment of OHSS is associated with significant costs to the healthcare system.14 In the UK for example, the cost of treating moderate and severe cases of OHSS is estimated to be over £7 million (over 9 million CHF) every year.14,15
About the ESTHER trials
The ESTHER trials (Evidence-based Stimulation Trial with Human recombinant FSH in Europe and Rest of World) were randomised, assessor-blind, controlled, multicentre Phase 3 trials.2,3
ESTHER-1 was a trial of 1,326 patients in 11 countries undergoing their first ART cycle. Patients were randomised 1:1 to receive treatment with individualised Rekovelle, a fixed daily dose based on serum AMH levels and body weight, or conventional follitropin alfa dosing. The co-primary endpoints of ongoing pregnancy rates and ongoing implantation rates were met and results showed no difference between the two treatment arms.2 Results of the ESTHER-1 trial were published in the February 2017 issue of Fertility & Sterility.2
ESTHER-2 evaluated the immunogenicity of Rekovelle in a subset of ESTHER-1 patients undergoing repeated cycles of COS for ART. Data demonstrated no increased immunogenicity risk with Rekovelle after exposure in repeated cycles.3
About Ferring Pharmaceuticals
Headquartered in Saint-Prex, Switzerland, Ferring Pharmaceuticals is a research-driven, specialty biopharmaceutical group active in global markets. A leader in reproductive and maternal health, Ferring has been developing treatments for mothers and babies for over 50 years. Today, over one third of the company’s research and development investment goes towards finding innovative treatments to help mothers and babies, from conception to birth. The company also identifies, develops and markets innovative products in the areas of urology, gastroenterology, endocrinology and orthopaedics. Ferring has its own operating subsidiaries in nearly 60 countries and markets its products in 110 countries, including Ferring AG based in Baar, Switzerland which was founded in 1984. Ferring AG is responsible for the distribution and marketing of Ferring products in Switzerland and Liechtenstein. For further information on Ferring or its products, visit www.ferring.com.
About the Elecsys® AMH Plus immunoassay from
The Elecsys® AMH Plus immunoassay from Roche has been shown to provide a precise, reliable and robust measurement of AMH levels.6,7,16,17,18,19 This fully automated Elecsys® AMH Plus immunoassay, run on the cobas® e and Elecsys® immunoassay analysers, determines AMH levels in 18 minutes, making it appropriate for routine clinical use. The Elecsys® AMH Plus immunoassay is intended to be used for assessment of ovarian reserve, prediction of response to COS and establishment of the individual daily dose of Ferring follitropin delta in combination with body weight in COS for the development of multiple follicles in women undergoing an assisted reproductive technology programme.1,6,7,16,17,18,19
* GONAL-f®, registered trademark of Merck KGaA, Darmstadt, Germany
† ESTHER-1 was neither designed nor powered to assess results based on secondary endpoints. Predefined secondary endpoints are used as a measurement to yield supportive evidence to evaluate additional effects relevant to informing the Rekovelle individualised dosing regimen. No confirmatory conclusions can be derived.
1 Rekovelle® Product Information, Switzerland.
2 Nyboe Andersen A, Nelson SM, Fauser BC, et al. Individualised versus conventional ovarian stimulation for an in vitro fertilization: a multicenter, randomized, controlled assessor-blinded, phase 3 noninferiority trial. Fertil Steril. 2017;107(2): 387-396.
3 Buur Rasmussen A, et al. Low immunogenicity potential of follitropin delta, a recombinant FSH preparation produced from a human cell line: Results from phase 3 trials (ESTHER-1 and ESTHER-2). Human Reproduction. 2016; 31: 385.
4 Olsson H, Sandström R, Grundemar L. Different pharmacokinetic and pharmacodynamic properties of recombinant follicle stimulating hormone (rFSH) derived from a human cell line compared with rFSH from a non-human cell line. J Clin Pharmacol. 2014; 54(11):1299–307.
5 Arce J-C, Nyboe Andersen A, Fernandez Sanchez M, et al. Ovarian response to recombinant human follicle stimulating hormone: a randomized, antimullerian hormone–stratified, dose–response trial in women undergoing in vitro fertilization/intracytoplasmic sperm injection. Fertil Steril. 2014;102(6): 1633–40.
6 Deeks ED. Elecsys® AMH assay: a review in anti-Müllerian hormone quantification and assessment of ovarian reserve. Mol Diagn Ther. 2015;19: 245-249.
7 Roche Diagnostics. Elecsys® AMH (anti-Mullerian hormone): Method sheet. 2015. http://www.cobas.com/content/dam/cobas_com/pdf/product/Elecsys%20AMH/Elecsys%20AMH%20FactSheet.pdf. [Last accessed October 2017].
8 Zegers-Hochschild F, Adamson GD, de Mouzon J, Ishihara O, Mansour R, Nygren K, Sullivan E, Van der Poel S. The international committee for monitoring assisted reproductive technology (ICMART) and the world health organization (WHO) revised glossary on ART terminology, 2009. Human reproduction. 2009;24(11): 2683-7.
9 La Marca A, Sighinolfi G, Radi D, et al. Anti-Mullerian hormone (AMH) as a predictive marker in assisted reproductive technology (ART). Hum Reprod Update. 2010;16(2): 113-130.
10 Mayo Clinic. OHSS Symptoms and Causes. Patient Care and Health Information. Available at: http://www.mayoclinic.org/diseases-conditions/ovarian-hyperstimulation-syndrome-ohss/symptoms-causes/dxc-20263586. [Last accessed: October 2017].
11 Salmassi A, Mettler L, et al.Cut-Off Levels of Anti-Mullerian Hormone for the Prediction of Ovarian Response, In Vitro Fertilization Outcome and Ovarian Hyperstimulation Syndrome. Int J Fertil Steril. 2015; 9(2): 157-167.
12 Delvigne A, Rozenberg S, et al. Epidemiology and prevention of ovarian hyperstimulation syndrome (OHSS): a review. Hum Reprod Update. 2002;8(6): 559-577.
13 Thomsen L, Humaidan P, et al. Ovarian hyperstimulation syndrome in the 21st century: the role of gonadotropin-releasing hormone agonist trigger and kisspeptin. Curr Opin Obstet Gynecol. 2015;27(3): 210-214.
14 Yates AP, Rustamov O, Roberts SA, et al. Anti-Mullerian hormone-tailored stimulation protocols improve outcomes whilst reducing adverse effects and costs of IVF. Hum Reprod. 2011;26(9): 2353-2362.
15 Human Fertilisation and Embryology Authority. Fertility Treatment in 2014 Trends and Figures Report. Available at: http://ifqtesting.blob.core.windows.net/umbraco-website/1111/hfea-fertility-treatment-trends-and-figures-2014.pdf [Last accessed: October 2017]
16 Gassner D, Jung R. First fully automated immunoassay for anti-Müllerian hormone. Clin Chem Lab Med. 2014;52(8): 1143-52.
17 Anderson RA, Anckaert E, Bosch E, et al. Prospective study into the value of the automated Elecsys antimüllerian hormone assay for the assessment of the ovarian growing follicle pool. Fertil Steril. 2015;103(4): 1074–80.e4.
18 Nelson SM, Pastuszek E, Kloss G, et al. Two new automated, compared with two enzyme-linked immunosorbent antimüllerian hormone assays. Fertil Steril. 2015;104(4):1016-1021.e6.
19 Hyldgaard J, Bor P, Ingerslev HJ, et al. Comparison of two different methods for measuring anti-mullerian hormone in a clinical series. Reprod Biol Endocrinol. 2015;13(1): 107.