The aim of the present study was to investigate the therapeutic equivalence between the follitropin alpha biosimilar and the reference medication in women undergoing assisted reproductive technologies (ART).
This multicenter, randomized (1:1), embryologist-blinded, parallel-group, comparative phase III study involved 110 women aged 20–35 years old with tubal and/or male factors of infertility. All of the subjects underwent controlled ovarian hyperstimulation (COH) using a gonadotropin-releasing hormone antagonist (GnRH-ant) protocol. Over the 5-day fixed-dose regimen, the women received 150 IU/day of follitropin alpha biosimilar (n = 55) or original follitropin alpha (n = 55), followed by dose adaptation. The primary endpoint for assessing the therapeutic equivalence was the number of retrieved oocytes using a pre-determined clinical equivalence margin of ± 3.4 oocytes.
Similar numbers of oocytes were retrieved in both groups: 12.16 ± 7.28 in the follitropin alpha biosimilar group and 11.62 ± 6.29 in the original follitropin alpha group, with mean difference of 0.546 ± 1.297 oocytes (95% confidence interval [CI]: -2.026, 3.116), p = 0.002 (intention-to-treat [ITT] population). Additionally, no statistically significant differences were found for secondary endpoints: the onset of biochemical (34.7% and 36.7%, p = 0.883), clinical pregnancy (26.5% and 32.7%, p = 0.507), delivery (26.5% and 24.5%, p = 0.817) and take-home baby rate (28.6% and 26.5%, p = 0.816) for the follitropin biosimilar and original follitropin groups (per-protocol [PP] population). Ovarian hyperstimulation syndrome was observed in subjects with a positive pregnancy test in 0% and 3.64% of cases and after triggering ovulation in 7.27% and 3.64% for the follitropin biosimilar and original follitropin groups, respectively.
This study demonstrated similar therapeutic equivalence and safety profiles between the follitropin alpha biosimilar and the reference follitropin in women who underwent COH in GnRH-ant cycles.
Trial registration number
1. Name of the registry: ClinicalTrials.gov. Trial registration number: NCT03088137. Date of registration: 02.03.2017, retrospectively registered. Trial conducted between 08.02.2017 and 17.08.2018, the date of enrollment of the first participant – 08.02.2017. 2. Name of the registry: Russian Ministry of Health, grls.rosminzdrav.ru. Trial registration number: RCT 754. Date of registration: 26.10.2016, prospectively registered.
Abbreviations:ART (assisted reproductive technology), IVF (in vitro fertilization), r-hFSH (recombinant human follicle-stimulating hormone), IU (International Units), OPU (ultrasound-guided follicular aspiration), AFC (antral follicle count), GnRH-ant (gonadotropin-releasing hormone antagonist), GnRH-a (gonadotropin-releasing hormone agonist), FSH (follicle-stimulating hormone), LH (luteinizing hormone), NIBSC (The National Institute for Biological Standards and Control), AMH (anti-Müllerian hormone), ITT (intent-to-treat), PP (per-protocol), CI (confidence interval), BMI (body mass index), ELISA (enzyme-linked immunosorbent assay), COH (controlled ovarian hyperstimulation), SC (subcutaneous), OHSS (ovarian hyperstimulation syndrome), ET (embryo transfer), PCOS (polycystic ovary syndrome), hCG (human chorionic gonadotropin), ICSI (intracytoplasmic sperm injection), PN (pronucleus), EMA (European Medicinal Agency), Neu5Gc (N-glycolyl neuraminic acid), CHO (Chinese hamster ovary)
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Published online: July 26, 2019
Accepted: July 24, 2019
Received in revised form: July 15, 2019
Received: February 12, 2019
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