SAINT-PREX, Switzerland--(BUSINESS WIRE)--Today, an oral poster of the first post-authorisation Phase 4 real-world study, PROFILE, is being presented at the 13th Congress of the Pacific Society for Reproductive Medicine (PSRM) 2023 in Australia. The large, prospective, multi-national study confirms the effectiveness and safety of Rekovelle in routine clinical practice, with ongoing pregnancy rates similar to Phase 3 RCTs.1-3,5 The study was first published in Frontiers of Endocrinology in December 2022.5
The PROFILE study enrolled 944 women who had not previously undergone in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI). Results highlighted that with Rekovelle, almost three-quarters (74.0%) of women had between 4-19 oocytes retrieved and 255 women (27.0%) achieved an ongoing pregnancy at 10-11 weeks after transfer. The ongoing pregnancy rate was similar to the rates observed in the Phase 3 RCTs.1–3 The first cycle cumulative ongoing pregnancy rate after fresh and/or frozen transfer was 36.4%. The research also showed a 3.9% incidence of ovarian hyperstimulation syndrome (OHSS), with most cases of OHSS being of mild to moderate intensity, (n=30 [3.2%]) and all participants with OHSS made a full recovery.5
“Up to now, we have more than 2,000 patients in the RCTs for Rekovelle – ESTHER-1 and -2, GRAPE and STORK trials – but these had strict inclusion and exclusion criteria. Real-world data extends efficacy and safety data to all patients. In fact, in PROFILE there were nearly no restrictions other than that the participants were seeking to become pregnant, had no contraindications to rFSH, and had not previously undergone ovarian stimulation,” said Professor Christophe Blockeel, from Brussels IVF, the Centre for Reproductive Medicine, Universitair Ziekenhuis Brussel and Vrije Universiteit Brussel, who was the principal investigator of the PROFILE study.
In countries where it is licensed, Rekovelle is the only rFSH for OS that has an individualised fixed daily dose calculated using an approved algorithm based on bodyweight and levels of AMH. AMH is a biomarker used to predict ovarian response.6 In PROFILE, physicians used the Rekovelle dosing algorithm for nearly all participants (95%), although some made minor adjustments to the prescribed starting dose or adjusted the dose during OS based on clinical factors. Adverse drug reactions (ADRs) were monitored for all initiated OS cycles, and the number of ADRs leading to treatment and study discontinuation was low (n=4).
“Ferring is committed to building healthy families of every shape and size by developing innovative fertility treatments. We are committed to seeking insights throughout the research and development of our treatments, so it is therefore encouraging to see that in an observational study of real-world clinical practice, Rekovelle confirmed its effectiveness through ongoing pregnancy rates, similar, or higher than RCTs,” said Christina Lloyd, Senior Vice President and Head of Reproductive Medicine and Maternal Health, Ferring Pharmaceuticals.
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About the PROFILE study
In the PROFILE study (Prospective multicentre non-interventional study to assess the patterns of use of Rekovelle in women undergoing in vitrO Fertilisation or Intracytoplasmic sperm injection procedures in routine clinicaL practicE), 1,258 women were screened between March 2018 and October 2020, and 1,013 met the inclusion and exclusion criteria. A total of 944 participants initiated their first OS cycle at 34 specialist fertility clinics across Australia, Austria, Belgium, Canada, Germany, Italy, Netherlands, Poland, Spain and UK in which Rekovelle is licensed. The primary endpoint was the real-world treatment patterns of follitropin delta, including starting daily dose, number of days of treatment, deviations from the approved dosing schedule as per the summary of product characteristics (per-label), use of dosing algorithm, and use of other treatments during OS, such as GnRH protocol, triggering methods of follicle maturation and luteal phase support. Secondary endpoints included cycle cancellations, pregnancy outcomes for Cycle 1, and OHSS and other ADRs for all initiated cycles. Participants could initiate up to three OS cycles with Rekovelle; however, utility and effectiveness data were only analysed for Cycle 1 as the study was terminated early due to the COVID-19 pandemic, during which many fertility clinics closed or provided reduced services.
Real-World Utilisation Patterns of Rekovelle
The study aimed to observe the real-world utilisation patterns, effectiveness, and safety profile of follitropin delta in women ≥18 years naïve to OS undergoing IVF or ICSI. According to the data collected during the study, most participants received Rekovelle as specified in the approved label without dose deviations. In PROFILE, nearly all patients (95%) had their starting dose calculated using the algorithm, although some physicians then made minor adjustments to the prescribed starting dose during the OS cycle based on clinical factors. “We wanted to know if physicians are really using the dosing algorithm, and the answer is yes, the vast majority did. I think this really reflects how Rekovelle is being used in the real world and physicians are using the algorithm in those countries where it is approved,” said Professor Blockeel. In PROFILE, the mean total dose of follitropin delta was slightly higher than observed in randomised clinical trials, reflecting differences in bodyweight and AMH levels of the participants.1-5 The PROFILE study had no enrolment restrictions for bodyweight or AMH levels, and the overall study population had a higher mean bodyweight and had lower or comparable median AMH levels than the RCT cohorts.1-3,5
Adverse Drug Reactions
ADRs were monitored for all initiated OS cycles (1,130 cycles for 944 participants). Forty-nine participants (5.2%) reported 58 ADRs. The number of ADRs leading to treatment and study discontinuation was low (four participants experiencing six ADRs: OHSS, n=2 events; vomiting, n=1 event; headache, n=1 event; rash, n=1 event and premature ovulation, n=1 event). The most frequent ADR was any grade of ovarian hyperstimulation syndrome (OHSS; n=37 [3.9%]), which was similar to the incidence of OHSS in the Rekovelle arm during the first cycle of the RCT ESTHER-1 (3.5%).1 In the PROFILE study, most cases of OHSS were of mild or moderate intensity (n=30 [3.2%]) and all participants with OHSS made a full recovery.
About Rekovelle (follitropin delta)
Rekovelle is a human rFSH with an approved dosing algorithm designed for a predictable ovarian response.7 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.7, 8 Rekovelle is approved in certain markets for use in OS for induction of the development of multiple follicles in women undergoing assisted reproductive technologies (ART), such as IVF or ICSI. The individualised dosing of Rekovelle is determined using an approved algorithm, based on a woman’s AMH level and body weight.7-9 AMH is a biomarker used to assess ovarian reserve and can help predict ovarian response.6 The Rekovelle dose should be based on AMH level, measured using the ELECSYS AMH Plus immunoassay from Roche, the ACCESS AMH Advanced from Beckman Coulter, or LUMIPULSE G AMH from Fujirebio.7 Rekovelle is not approved in all markets.
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 employs over 7,000 people worldwide. The company has operating subsidiaries in more than 50 countries and markets its products in over 100 countries.
1. Nyboe Andersen A, Nelson SM, Fauser BC, Garcia-Velasco JA, Klein BM, Arce JC, et al. Individualized versus conventional ovarian stimulation for in vitro fertilization: a multicenter, randomized, controlled, assessor-blinded, phase 3 noninferiority trial. Fertil Steril. 2017 Feb;107(2):387-96 e4. PubMed PMID: 27912901. Epub 2016/12/04.
2. Qiao J, Zhang Y, Liang X, Ho T, Huang HY, Kim SH, et al. A randomised controlled trial to clinically validate follitropin delta in its individualised dosing regimen for ovarian stimulation in Asian IVF/ICSI patients. Hum Reprod. 2021 Jun 28;36(9):2452-62. PubMed PMID: 34179971. Epub 2021/06/29.
3. Ishihara O, Arce JC, Japanese Follitropin Delta Phase 3 Trial G. Individualized follitropin delta dosing reduces OHSS risk in Japanese IVF/ICSI patients: a randomized controlled trial. Reprod Biomed Online. 2021 May;42(5):909-18. PubMed PMID: 33722477. Epub 2021/03/17.
4. Bosch E, Havelock J, Martin FS, Rasmussen BB, Klein BM, Mannaerts B, et al. Follitropin delta in repeated ovarian stimulation for IVF: a controlled, assessor-blind phase 3 safety trial. Reprod Biomed Online. 2019 Feb;38(2):195-205. PMID: 30594482. Epub 2018/12/14.
5. Blockeel C, Griesinger G, Rago R, Larsson P, Sonderegger YLY, Rivière S, et al. Prospective multicenter non-interventional real-world study to assess the patterns of use, effectiveness and safety of follitropin delta in routine clinical practice (the PROFILE study). Frontiers in Endocrinology. 2022 Dec 22;13:992677. PMID: 36619578.
6. Arce JC, La Marca A, Mirner Klein B, Nyboe Andersen A, Fleming R. Antimullerian hormone in gonadotropin releasing-hormone antagonist cycles: prediction of ovarian response and cumulative treatment outcome in good-prognosis patients. Fertil Steril. 2013 May;99(6):1644-53. PubMed PMID: 23394782. Epub 2013/02/12.
7. Follitropin Delta (Rekovelle) Summary of Product Characteristics. Date of publication 2016. Approved on 12 December 2016 and last updated on the EMA website in March 2022. Available from https://www.ema.europa.eu/en/documents/productinformation/rekovelle-eparproduct-information_en.pdf [Accessed March 2023].
8. Olsson H, Sandstrom 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 Nov;54(11):1299-307. PubMed PMID: 24800998. Epub 20140521.
9. Arce JC, Andersen AN, Fernandez-Sanchez M, Visnova H, Bosch E, Garcia-Velasco JA, 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 e5. PubMed PMID: 25256937. Epub 2014/09/27.
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