1Raoul Orvieto MD, MMSc and 2David B. Seifer MD
1Infertility and IVF Unit, Department of Obstetrics and Gynecology, Chaim Sheba Medical Center (Tel Hashomer), Ramat Gan, Israel and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
2Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Dartmouth-Hitchcock Medical Center, Geisel School of Medicine at Dartmouth, Lebanon, NH, USA
We thank Strowitzki et al. for their letter. The editorial was not meant to be negative to any product (biosimilar or the reference products), or to recommend against the use of biosimilar products in clinical practice, but to describe the biological differences between the products and to provide a brief overview of the published clinical studies.
Biosimilars are legitimate products, and are a welcomed addition to the FSH armamentarium. We have not “questioned the legal basis” of biosimilar registration, but rather, have called for caution while implementing a new product to the COH armamentarium. As we have already stated and clearly described, since biosimilars are not identical to the reference products, and due to the fact that the clinical experience gained with their use came from RCT’s which included “ideal”, best prognosis patients, we believe that for patients’ safety, “further comparative studies are needed in other patient populations that are encountered during routine daily clinical practice, e.g., older, poor responders, patients with repeated IVF failures or high responders, such as those with polycystic ovary syndrome, before the universal implementation of biosimilar products to clinical use”. Moreover, this is also why we recommend “against interchanging or substituting innovator and biosimilar agents in clinical practice, and believe that the decision whether to use an innovator or a biosimilar product, should be reserved to the discretion of the treating physician”.
Specific comments:
We do not doubt, neither did we attempt to challenge the legitimacy of the biosimilar products registration, the EMA regulations or decisions. As mentioned above, biosimilars are legitimate products and are a welcomed addition to the FSH armamentarium.
The fact the RCTs (those supporting the use of Gonal-f and Puregon) were conducted in “ideal” patients, does not mean that caution should not be taken while treating “non-ideal” patients.
The clinical data, as presented in the Editorial, summarized the two RCT’s and did not mean to replace them. As stated, Table 2 simply gathered the data from the 2 RCTs and was not meant to conduct a sophisticated statistical analysis. Its intent was to support the notion that biosimilars are not “identical twins”. Moreover, the cancellation rate was non-significantly lower in the Gonal-f, as compared to the Bemfola group. No mention was made in the Editorial regarding cancellation rate in the Ovaleap Study.
We thank Strowitzki et al. for their correction regarding the oocyte number (which was stated correctly in the table, but not in the text). An erratum has been published accordingly.