Saint-Prex, Switzerland – 17 October 2016 – Ferring Pharmaceuticals announced today that the Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion for REKOVELLE® (follitropin delta), recommending that the European Commission grants marketing authorisation 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.1-3The European Commission has authority to grant marketing authorisation for medicines in the 28 countries of the European Union (EU). Following a European Commission decision, authorisation can also be granted by national authorities in Norway and Iceland.
If approved, REKOVELLE® would be administered using an individualised dosing regimen according to a woman’s serum anti-Müllerian hormone (AMH) level and her body weight. AMH is a biomarker used to assess ovarian reserve.4,5 This can help to predict ovarian response to controlled ovarian stimulation and thus identify patients who may be at higher risk of experiencing reduced efficacy or increased safety concerns.4,6,7 The individualised dosing regimen determines a specific daily dose of REKOVELLE® for each patient, with the aim of maintaining efficacy and improving safety during controlled ovarian stimulation. AMH would be measured by a companion diagnostic, the Elecsys® AMH Plus immunoassay from F. Hoffmann-La Roche Ltd (Roche).8,9
“The individualised dosing regimen for REKOVELLE® aims to further enrich the personalised care that fertility specialists offer their patients,” said Dr Per Falk, M.D. Ph.D., Chief Scientific Officer and Executive Vice President at Ferring Pharmaceuticals. “If approved, this would be the first pairing of a drug with a companion diagnostic for individualised dosing in reproductive medicine.”
The CHMP positive opinion is based on 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 1,326 patients in 11 countries, and over 2,000 cycles of controlled ovarian stimulation.1-3,10,11
Non-inferiority was demonstrated in a Phase 3 trial for the co-primary endpoints of ongoing pregnancy rate and ongoing implantation rate for REKOVELLE® compared to follitropin alfa (conventional treatment and dosing regimen). Secondary endpoints, including the number of oocytes retrieved and number of blastocysts obtained, were comparable between both groups. The Phase 3 clinical trials also demonstrated no increased immunogenicity risk and a good safety profile for REKOVELLE® with repeated cycles of controlled ovarian stimulation.3,11
About REKOVELLE® (follitropin delta)
Follitropin delta (also known as FE 999049) is the first recombinant follicle stimulating hormone (FSH) derived from a human cell line.1,12 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,1,5,6,8,9 and her body weight. Follitropin delta is structurally and clinically distinct from other existing recombinant FSH treatments.1,12
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 involving fertility clinics in Europe, Canada, Brazil and Russia.2,3
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.8,9,13-16 This fully automated Elecsys® AMH Plus immunoassay uses 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 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 program.8,9,13-16
For more information
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- 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.
- ESTHER-1 trial. www.clintrials.gov Available at: https://clinicaltrials.gov/ct2/show/NCT01956110. Last accessed: September 2016.
- ESTHER-2 trial. www.clintrials.gov. Available at: https://clinicaltrials.gov/ct2/show/NCT01956123. Last accessed: September 2016
- 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.
- La Marca A and Sunkara SK. Individualization of controlled ovarian stimulation in IVF using ovarian reserve markers: from theory to practice. Hum Reprod Update 2014;20: 124–140.
- American Society for Reproductive Medicine. Medications for Inducing Ovulation - A guide for patients. Available here. Last accessed: September 2016.
- Nelson SMet al. Anti-Müllerian hormone-based approach to controlled ovarian stimulation for assisted conception. Hum Reprod. 2009 Apr;24(4):867–75.
- Deeks ED. Elecsys® AMH assay: a review in anti-Müllerian hormone quantification and assessment of ovarian reserve. Mol Diagn Ther 2015; 19: 245-249.
- Roche Diagnostics. Elecsys® AMH Plus: Method sheet. 2016.
- Nyboe Andersen A and Arce JC on behalf of the ESTHER-1 trial group. 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). Poster presented at 32nd Annual Meeting of the European Society of Human Reproduction and Embryology (ESHRE) in Helsinki, 3–6 July 2016. Hum Reprod. 2016;31(Supp 1):i315.
- Buur Rasmussen A et al, on behalf of the ESTHER-1 and ESTHER-2 trial group. 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). Poster presented at 32nd Annual Meeting of the European Society of Human Reproduction and Embryology (ESHRE) in Helsinki, 3–6 July 2016. Hum Reprod. 2016;31(Supp 1):i376.
- 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.
- Gassner D, Jung R. First fully automated immunoassay for anti-Müllerian hormone. Clin Chem Lab Med. 2014;52(8):1143-52.
- 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.
- 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.
- 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.