SAINT PREX, Switzerl--(뉴스와이어)--New data, presented today at the 37th Annual Meeting of the European Society of Human Reproduction and Embryology (ESHRE), show a comparable ongoing pregnancy rate of 31.3% with the individualised dosing regimen of Rekovelle, compared to 25.7% with follitropin alfa (adjusted difference 5.4% [95% CI:-0.2%; 11.0%]) amongst all ages in an Asian study population (mainland China, South Korea, Vietnam and Taiwan). [1]The live birth rate was significantly higher at 31.3% with Rekovelle compared to 24.7% with follitropin alfa (adjusted difference 6.4% [95% CI: 0.9%; 11.9%]; p<0.05). This was a pre-defined secondary endpoint so no confirmatory conclusions can be drawn.[1]

In the GRAPE study (a randomised, controlled, assessor-blind pan-Asian trial comparing individualised Rekovelle (follitropin delta) with conventional follitropin alfa), comparable pregnancy rates were achieved alongside a significant reduction in early OHSS incidence (5.0% with Rekovelle versus 9.6% with follitropin alfa). Among patients with AMH ≥15 pmol/L, excessive response occurred less frequently with individualised than conventional dosing (≥15 oocytes: 20.2% versus 39.1%; ≥20 oocytes: 6.7% versus 18.5%).[1] These secondary data endpoints support previous studies which have found that individualised Rekovelle dosing reduces the risk of ovarian hyperstimulation syndrome (OHSS) and interventions to prevent it versus the conventional approach.[4,5]

“These data imply that, in addition to reducing the early OHSS risk, individualised dosing with follitropin delta has the potential to increase the live birth rate in fresh cycle across all ages,” said Professor Jie Qiao, Academician of Chinese academy of engineering, Vice President of China Association for science and technology, Executive Vice President of Peking University, Director of Peking University Health Science Center, President of Peking University Third Hospital, Academician of American Academy of Arts and Sciences (IHM). “The data offer - for the first time - important support for the use of this treatment in the Asian population.”

A new, independent individual patient data - meta-analysis (IPD-MA) of nearly 2,700 women randomised to a conventional dosing regimen with follitropin alfa or beta, or individualised dosing with Rekovelle, supports the above findings.[2] The occurrence of early OHSS was significantly reduced in the individualised Rekovelle group (4% vs. 6.4%). The study found that live birth rates were comparable in individuals who received individualised Rekovelle treatment compared to those who received follitropin alfa or beta. Moreover, the live birth rate in normal to high responders was significantly increased in those receiving individualised Rekovelle (31.4% vs. 25.9%).[2] “The results of the IPD-MA support previous data which has shown that an individualised follitropin delta dosing regimen reduces the risk of OHSS without compromising efficacy,” said Dr Femi Janse of the Nij Barrahus Fertility Clinic. “They also offer insights for clinicians seeking to tailor their treatment approach for normal and high responder patients.”

Additional analysis from the ESTHER-1 and 2 clinical trials - also announced at this year’s ESHRE - show that Rekovelle and follitropin alfa dosing regimens were non-inferior in terms of live birth rate in frozen replacement cycles.[3] The analysis of 917 women who participated in the ESTHER-1 and 2 trials found that the live birth rate per started frozen cycle was 32.0% in the Rekovelle group and 31.3% in the follitropin alfa group (adjusted difference 1.2% [95% CI: -6.8%; 9.3%]).[3]

“At Ferring we believe in everyone’s right to a family, so are pleased to announce emerging data showing the benefits of the individualised Rekovelle dosing regimen in new populations and patient groups,” said Mirjam Mol-Arts, Chief Medical and Science Officer at Ferring. “In addition, the expanded AMH assay options now included in the EU label are additional features allowing expansion of current treatment boundaries.”

About the GRAPE study[1]

GRAPE was a randomised, controlled, assessor-blind pan-Asian trial comparing individualised Rekovelle (follitropin delta) with conventional follitropin alfa. The primary endpoint was ongoing pregnancy rate assessed 10-11 weeks after transfer. The trial found an ongoing pregnancy rate per started cycle of 31.3% for individualised Rekovelle vs 25.7% for conventional follitropin alfa. The live birth rate per started cycle was significantly higher for individualised Rekovelle than for conventional follitropin alfa. Early OHSS risk, evaluated as the incidence of early OHSS and/or preventive interventions, was significantly reduced with Rekovelle.

About the meta-analysis[2]

This was an independent individual patient data - meta-analysis (IPD-MA) of three Rekovelle (follitropin delta) phase 3 trials to investigate whether an individualised, weight and AMH-based dosing approach with Rekovelle improved live birth rate, safety and efficiency compared to conventional dosing in IVF / ICSI. The study found that individualised dosing with Rekovelle was similarly effective in terms of live birth rate (with significantly higher live birth rates seen in normal to high responders) and reduced safety risks and total follicle-stimulating hormone (FSH) dosage compared to conventional dosing in IVF/ICSI.

About the analysis of the ESTHER-1 and 2 trials[3]

This analysis reviewed frozen cycles using blastocysts obtained from a randomised trial comparing individualized dosing with Rekovelle (follitropin delta) versus conventional dosing with follitropin alfa in 1,326 IVF/ICSI patients (ESTHER-1), and a subsequent trial of up to two additional ovarian stimulation cycles (ESTHER-2), for women who did not achieve pregnancy in ESTHER-1. This analysis aimed to compare the live birth rate using frozen-thawed blastocysts obtained from ovarian stimulation with individualized Rekovelle dosing and conventional follitropin alfa dosing. The proportion of women with frozen blastocysts was similar in the two treatment groups. Similar freeze-thaw blastocyst survival rates were observed for the two groups, as were implantation rate and live birth rates.

About Rekovelle (follitropin delta)

Rekovelle is a human recombinant follicle stimulating hormone (rFSH) with an approved dosing algorithm designed for predictable ovarian response.[6] It is the first rFSH derived from a human cell line (PER.C6® cell line). Rekovelle is structurally and biochemically distinct from other existing rFSH gonadotrophins.[6,7] Rekovelle is approved for use in ovarian stimulation (OS) 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). The individualised dosing of Rekovelle is determined using an approved algorithm, based on a woman’s anti-Müllerian hormone (AMH) level and body weight.[4,6,8] AMH is a biomarker used to assess ovarian reserve and can help predict ovarian response. AMH will be measured with a companion diagnostic, the ELECSYS AMH Plus immunoassay from F. Hoffmann-La Roche Ltd (Roche), or alternatively the ACCESS AMH Advanced from Beckman Coulter or LUMIPULSE G AMH from Fujirebio.[9,10]

About Ferring Pharmaceuticals

Ferring Pharmaceuticals is a research-driven, specialty biopharmaceutical group committed to helping people around the world build families and live better lives. Headquartered in Saint-Prex, Switzerland, Ferring is a leader in reproductive medicine and maternal health, and in specialty areas within gastroenterology and urology. Ferring has been developing treatments for mothers and babies for over 50 years and has a portfolio covering treatments from conception to birth. Founded in 1950, privately-owned Ferring now employs around 6,000 people worldwide, has its own operating subsidiaries in nearly 60 countries and markets its products in 110 countries.

Learn more at www.ferring.com, or connect with us on Twitter, Facebook, Instagram, LinkedIn and YouTube.

References:

1. Qiao J, Zhang Y, Liang X, Ho T, Huang H-Y, Kim S-H, Goethberg M, Mannaerts B, and Arce J-C, on behalf of the Asian Follitropin Delta Phase 3 Trial (GRAPE) Group. A randomised controlled trial to clinically validate follitropin delta in its individualised dosing regimen for ovarian stimulation in Asian IVF/ICSI patients. Human Reproduction. June 2021. DOI: https://doi.org/10.1093/humrep/deab155

2. Janse F, Eijkemans M, Fauser B. Improved safety and efficiency of individualised versus conventional gonadotropin dosing for ovarian stimulation in IVF/ICSI: an individual patient meta-analysis (IPD-MA)

3. Havelock J, Arce JC. Clinical outcome in frozen cycles using cryopreserved blastocysts derived from ovarian stimulation with follitropin Delta. Abstract presented at ESHRE 2021.

4. Andersen AN et al. Individualized versus conventional ovarian stimulation for in vitro fertilization: a multicenter, randomized, controlled, assessor-blinded, phase 3 noninferiority trial. Fertil Steril. 2017;107(2):387-396.

5. Isihara O. et al. Individualized follitropin delta dosing reduces OHSS risk in Japanese IVF/ICSI patients: a randomized controlled trial. eprod Biomed Online. 2021;42(5):909-918.

6. Rekovelle® Summmary of Product Characteristics. Date of publication 2016 12 [cited 14 June 2018]. Approved on 18 March 2021 and made available on the EMA website on 17 May 2021: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR__Summary_for_the_public/human/003994/WC500220238.pdf.

7. 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. Journal of Clinical Pharmacology. 2014 11 [cited 2018 Jun 14];54(11):1299-307.

8. Arce JC, Nyboe Andersen A, Fernandez Sanchez M, et al. Ovarian response to recombinant human follicle stimulating hormone: a randomized, anti-Müllerian hormone-stratified, dose-response trial in women undergoing in vitro fertilization/intracytoplasmic sperm injection. Fertility and Sterility. 2014 12 [cited 2018 Jun 14];102(6):1633-164

9. Deeks ED. Elecsys® AMH assay: a review in anti-Müllerian hormone quantification and assessment of ovarian reserve. Molecular Diagnosis & Therapy. 2015 07 [cited 2018 Jun 14];19: 245-249.

10. Roche Diagnostics. Elecsys® AMH (anti-Müllerian hormone): Method sheet. (2015). Date of publication 2014 [cited 2018 Jun 14]. Available from: http://www.cobas.com/content/dam/cobas_com/pdf/product/Elecsys%20AMH/Elecsys%20AMH%20FactSheet.pdf.

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