Abstract
Study question
Are safety and effectiveness of Ovaleap® (follitropin alfa), and Gonal-f®, comparable in one treatment cycle of ART in routine clinical practice?
Summary answer
Safety in terms of incidence proportions of OHSS and OHSS severity, as well as pregnancy and live birth rates, were similar between Ovaleap® and Gonal-f®.
What is known already
Ovaleap® (Theramex), a r-hFSH, is a biosimilar medicinal product to Gonal-f® (Merck). As a biosimilar, it went through a rigorous series of physio-chemical, in vitro, in vivo tests and confirmatory Phase I and III studies, to demonstrate similarity/equivalence in quality, safety and efficacy to the reference medicinal product, per the European Medicines Agency (EMA) guidelines. Ovaleap® was approved by the EMA in 2013 for use at the same dose and for the same therapeutic indications as Gonal-f®. Further outcome data from a broader patient population on safety and live birth outcomes provides clinically important insights on newly introduced FSH medicines.
Study design, size, duration
SOFIA (Safety of Ovaleap® Follitropin alfa in Infertile women undergoing superovulation for Assisted reproductive technologies) was a multi-national, comparative, non-interventional, prospective cohort study. The study was performed at 56 centers specializing in ART from six European countries, (Belgium, France, Germany, Italy, Spain, and the United Kingdom) from January 2017 to September 2019 and comprised of 817 infertile women undergoing controlled ovarian hyperstimulation in one treatment cycle for ART
Participants/materials, setting, methods
The study population comprised of infertile women undergoing controlled ovarian hyperstimulation for ART, who were administered Ovaleap® or Gonal-f® and were naïve to any FSH containing products. Eligible patients were enrolled at a ratio of approximately 1:1, both within and between countries. They were followed up to 30 days after the last FSH dose administration. Women who had a confirmed clinical pregnancy were followed until the end of the pregnancy or until delivery.
Main results and the role of chance
A total of 408 and 409 women who were administered Ovaleap® or Gonal-f®, respectively, were eligible for analysis. A total of 382 patients (94%) in the Ovaleap® and 390 patients (95%) in the Gonal-f® cohort completed FSH treatment (up to oocyte maturation triggering), respectively. The two cohorts were generally similar with regard to demographic and baseline characteristics. The incidence proportion of OHSS was 5.1% (95% CI: 3.4, 7.7) in the Ovaleap® and 3.2% (95% CI: 1.9, 5.4) in the Gonal-f® cohort. This difference in OHSS incidence proportion between the two cohorts was not statistically significant neither before (p = 0.159) nor after univariate adjustment for each potential confounder (p > 0.05). The incidence proportion of OHSS severity grades was similar in the two treatment groups (3.4% versus 2.0% for Grade I, 1.2% versus 1.0% Grade II, and 0.5% versus 0.2% Grade III, in the Ovaleap® and Gonal-f® cohorts, respectively) and without a significant statistical difference (p = 0.865, for each grade). Among patients who had embryo transfer, clinical pregnancy rates were 33% and 31%, live birth rates 27% and 26% in the Ovaleap® and Gonal-f® cohorts, respectively.
Limitations, reasons for caution
Since treatment was non-randomised, the study may have been susceptible to selection bias. This was addressed at both the design stage, by balancing recruitment to a 1:1 ratio for Ovaleap® and Gonal-f® treatments, and also at the analysis stage in which, a univariate analysis was performed.
Wider implications of the findings: Findings from this first large European prospective comparative real-world SOFIA study demonstrated that effectiveness (pregnancy and delivery rates) and safety (risk and severity of OHSS), were similar between Ovaleap®and Gonal-f® treatments. Ovaleap, a biosimilar r-hFSH is therefore a suitable option for follicular stimulation in routine clinical practice.
Trial registration number
EUPAS17328
Effectiveness and safety of follitropin alfa (Ovaleap®) for ovarian stimulation using a GnRH antagonist protocol in real-world clinical practice: a multicenter, prospective, open, non-interventional assisted reproductive technology study
