Saint-Prex, Switzerland - 4 July 2016 - Data from the Phase 3 ESTHER trials (Evidence-based Stimulation Trial with Human recombinant follicle-stimulating hormone (FSH) in Europe and Rest of World) were presented today at the 32nd Annual Meeting of the European Society of Human Reproduction and Embryology (ESHRE) in Helsinki, Finland.
ESTHER-1, a randomised, assessor-blind, controlled, multicentre trial in women aged 18–40 years undergoing their first cycle of in-vitro fertilisation (IVF) or intracytoplasmic injection (ICSI) assessed an individualised dosing regimen of follitropin delta compared to follitropin alfa (conventional dosing regimen) .1
The individualised dosing regimen for follitropin delta was based on the patient’s serum anti-Müllerian hormone (AMH) level (a parameter used to assess ovarian reserve) and body weight. This individualised dosing regimen was used from the first day of controlled ovarian stimulation to determine an appropriate dose of FSH with the aim of minimising the risk of poor and excessive ovarian response in IVF or ICSI.1,2
Non-inferiority was demonstrated for the co-primary endpoints of ongoing pregnancy rate (30.7% vs 31.6%; LL 95% CI -5.9%) and ongoing implantation rate (35.2% vs 35.8%; LL 95% CI -6.1%) for follitropin delta compared to follitropin alfa.1
Secondary endpoints, including the number of oocytes retrieved and number of blastocysts obtained, were comparable between both groups. In addition, ovarian hyperstimulation syndrome (OHSS) and/or OHSS preventive interventions occurred less frequently (p<0.05) in women receiving follitropin delta than in women in the follitropin alfa group.1
“This trial is an integral part of Ferring’s commitment to help couples conceive by translating the practice of personalised medicine into reproductive health and fertility,” commented Joan-Carles Arce, M.D., Ph.D., Vice President Clinical Research & Development, Ferring. “We believe that by focusing on innovative and personalised approaches to treatment, we can continue to lead the way in assisted reproductive technology.”
Additional data from the ESTHER-2 trial presented at the meeting demonstrated no increased immunogenicity risk following controlled ovarian stimulation with follitropin delta after exposure in repeated cycles.3
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About the ESTHER trials
The ESTHER trials were randomised, assessor-blind, controlled, multicentre trials involving fertility clinics in Europe, Canada, Brazil and Russia.4,5
The ESTHER-1 trial established non-inferiority for ongoing pregnancy rates and ongoing implantation rates for follitropin delta (individualised dosing regimen) compared to follitropin alfa (conventional dosing regimen), in women undergoing their first IVF/ICSI cycle. The trial randomised 1,326 women aged 18–40 years to either a daily, individualised dose of follitropin delta which was fixed throughout stimulation, or a daily follitropin alfa dose of 150 IU (11 µg) for the first five days, which could thereafter be adjusted by the investigator according to the patient’s response.
- Non-inferiority was established for ongoing pregnancy rate (30.7% vs 31.6%; LL 95% CI -5.9%) and ongoing implantation rate (35.2% vs 35.8%; LL 95% CI -6.1%) for follitropin delta compared to follitropin alfa.
- The number of oocytes retrieved was similar for follitropin delta and follitropin alfa in the overall population (10.0 and 10.4, respectively).
- More (p<0.05) patients using the fixed, individualised dosing regimen of follitropin delta obtained the target 8–14 oocytes, as compared to those using the conventional dosing regimen of follitropin alfa. This is despite dose adjustments in 36.8% of follitropin alfa patients. As requested by the protocol, there was no dose adjustment in the follitropin delta group.
- OHSS preventive interventions occurred less frequently (p<0.05) in patients receiving an individualised dose of follitropin delta than in patients in the follitropin alfa group.
- The number of blastocysts obtained was comparable between follitropin delta and follitropin alfa (3.3 and 3.5, respectively).
In the ESTHER-2 trial, a subset of women underwent additional assessor-blind stimulation cycles (a total of 513 in cycle 2, and 188 in cycle 3). In all treatment cycles, blood samples for anti-FSH antibody analyses were collected at stimulation day 1 (pre-dosing) as well as 7–10 days (first post-dosing) and 21–28 days (second post-dosing) after the last gonadotropin dose.
- No increased immunogenicity risk was found following COS with follitropin delta, neither in the first treatment cycle nor after exposure in repeated cycles.
- The incidence of anti-FSH antibodies prior to exposure to follitropin delta was 1.4% after treatment. With follitropin delta, the incidence of anti-FSH antibodies was 1.1% in cycle 1, 0.8% in cycle 2 and 1.1% in cycle 3.
- These incidences were similar to those observed for follitropin alfa.
About follitropin delta
Follitropin delta (also known as FE 999049) is the first recombinant FSH derived from a human cell line (human rFSH), and has been developed for individualised dosing based on serum AMH level and body weight.1,6 Follitropin delta is structurally and clinically distinct from other existing recombinant follicle stimulating hormone treatments.6,7
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.
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- 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.
- 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.
- 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.
- ESTHER-1 trial. www.clintrials.gov Available at: https://clinicaltrials.gov/ct2/show/NCT01956110. Last accessed: June 2016.
- ESTHER-2 trial. www.clintrials.gov. Available at: https://clinicaltrials.gov/ct2/show/NCT01956123. Last accessed: June 2016.
- 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.
- 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.
Please note that this press release does not imply endorsement by ESHRE®