Saint-Prex, Switzerland – 13 December 2016 – Ferring Pharmaceuticals announced today that the European Commission (EC) has granted marketing authorisation for REKOVELLE® (follitropin delta), a human recombinant follicle stimulating hormone (human rFSH), for use in controlled ovarian stimulation for the development of multiple follicles in women undergoing assisted reproductive technologies (ART), such as an in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI) cycle.1
REKOVELLE® is the first rFSH to be derived from a human cell line and is the first rFSH treatment to be administered with an individualised dosing regimen.1-5 REKOVELLE®’s individualised dosing regimen is based on a woman’s serum anti-Müllerian hormone (AMH) level and her body weight. With these parameters, a specific daily dose of REKOVELLE® is determined for each patient from the start of the ART cycle.1-4,6,7 AMH has surfaced as one of the most reliable biomarkers for assessing ovarian reserve.It can help predict a woman’s ovarian response to gonadotrophin stimulation and can also help guide the dosing of fertility treatments.8,9 AMH will be measured by a companion diagnostic, the Elecsys® AMH Plus immunoassay from F. Hoffmann-La Roche Ltd (Roche).6,7
The EC approval of REKOVELLE® is based on a comprehensive clinical data package, including results from the Phase 3 ESTHER trials (Evidence-based Stimulation Trial with Human rFSH in Europe and Rest of World).2-4 Results of the ESTHER-1 trial were accepted for publication in Fertility & Sterility (article in press and available early online). The data shows that individualised treatment with REKOVELLE® (follitropin delta), as compared to treatment with conventional rFSH (follitropin alfa), had similar results for the co-primary endpoints of ongoing pregnancy rates and ongoing implantation rates. Patients receiving REKOVELLE® also reached the optimum oocyte yield (8–14 oocytes) more often than those receiving conventional rFSH treatment, with fewer clinically-relevant instances of poor and excessive ovarian response. In addition, ovarian hyperstimulation syndrome (OHSS) and/or OHSS preventive interventions occurred less frequently (p<0.05) in women receiving REKOVELLE® than women receiving conventional rFSH treatment.4
“REKOVELLE®’s individualised dosing regimen offers physicians a new method to deliver a consistent, evidence-based approach to personalising treatment for their patients, based on AMH, a highly predictive biomarker,” commented Professor Anders Nyboe Andersen, Principal Investigator of the ESTHER trials. “Using validated protocols for individualisation could help physicians facilitate the best possible outcomes for their patients by ensuring efficacy is maintained while also reducing complications during treatment.”
REKOVELLE® is an integral part of Ferring’s commitment to translating the practice of personalised medicine into reproductive health and fertility. “Ferring has a long-standing commitment to scientific advancement in reproductive health,” said Michel Pettigrew, President of the Executive Board and COO at Ferring Pharmaceuticals. “As a research-driven company, we believe that by focusing on innovative and personalised approaches, we can continue to lead the way in fertility treatments and help women to plan their futures as mothers.”
About REKOVELLE® (follitropin delta)
Follitropin delta (also known as FE 999049) is the first recombinant follicle stimulating hormone (rFSH) derived from a human cell line (PER.C6® cell line).1-4,5,10 It has been developed for individualised dosing based on a woman’s serum anti-Müllerian hormone (AMH) level, as determined by a companion diagnostic, the Elecsys® AMH Plus immunoassay from Roche,4,6,7 and her body weight. Follitropin delta is structurally and biochemically distinct from other existing recombinant FSH treatments.1-4,5,10
About the ESTHER trials
The ESTHER trials (Evidence-based Stimulation Trial with Human rFSH in Europe and Rest of World) were randomised, assessor-blind, controlled, multicentre Phase 3 trials involving patients in 11 countries, and over 2,000 cycles of controlled ovarian stimulation.2-4
About Ferring Pharmaceuticals
Headquartered in Switzerland, Ferring Pharmaceuticals is a research-driven, specialty biopharmaceutical group, active in global markets. The company identifies, develops and markets innovative products in the areas of reproductive health, urology, gastroenterology, endocrinology and orthopaedics. Ferring has its own operating subsidiaries in nearly 60 countries and markets its products in 110 countries. To learn more about Ferring or its products please visit www.ferring.com.
About the Elecsys® AMH Plus immunoassay from Roche
The Elecsys® AMH Plus immunoassay from Roche has been shown to provide a precise, reliable and robust measurement of AMH levels.6,7,11-14 This fully automated Elecsys® AMH Plus immunoassay, run on the cobas® e systems and the 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 controlled ovarian stimulation (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.6,7,11-14
For more information
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1. REKOVELLE® Summary of Product Characteristics (SmPC) – Available upon request.
2. Nyboe Andersen A et al. Efficacy and safety of follitropin delta in an individualised dosing regimen: A randomised, assessor-blind, controlled phase 3 trial in IVF/ICSI patients (ESTHER-1). Human Reproduction 2016; 31: 324
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. Nyboe Andersen A et al. Individualized versus conventional ovarian stimulation for in vitro fertilization: a multicenter, randomized, controlled, assessor-blinded, phase 3 noninferiority trial. Fertil Steril. In press, available early online. doi.org/10.1016/j.fertnstert.2016.10.033
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 Dec;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. https://pim-eservices.roche.com. Last accessed Novemober 2016.
8. Nelson SM et al. Anti-Müllerian hormone-based approach to controlled ovarian stimulation for assisted conception. Hum Reprod. 2009 Apr;24(4):867–75.
9. Fleming R, Broekmans F, Calhaz-Jorge C, et al. Can anti-Mullerian hormone concentrations be used to determine gonadotropin dose and treatment protocol for ovarian stimulation? Reproductive BioMedicine Online 2013;26:431–439.
10. 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.
11. Gassner D, Jung R. First fully automated immunoassay for anti-Müllerian hormone. Clin Chem Lab Med. 2014;52(8):1143-52.
12. 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.
13. Nelson SM, Pastuszek E, Kloss G, et al. Two new automated, compared with two enzyme-linked immunosorbent antimüllerian hormone assays. Fertil Steril. 2015 Oct;104(4):1016-1021.e6.
14. 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 Sep 22;13(1):107.