The European risk management plan (RMP) contains relevant safety information for specific products, with characterizations of both potential and identified risks, including real-world data. Because the RMP is systematically updated, the RMP can provide early indications of differences in product safety between originator and biosimilar therapies.
The European Union has had over a decade of experience with biosimilar therapies, and has collected real-world data concerning the use of these therapies in routine practice. A new study, accepted for publication in the British Journal of Clinical Pharmacology, used the European Union’s risk management plan (RMP) for biosimilars and corresponding reference biologics to compare the safety of these therapies, and found no substantial differences in reported safety.
The European RMP contains relevant safety information for specific products, with characterizations of both potential and identified risks, including real-world data. Because the RMP is systematically updated, the RMP can provide early indications of differences in product safety between originator and biosimilar therapies.
The researchers used a cross-sectional analysis of publicly available documents of biosimilars and their originator products for biosimilars authorized between January 2005 and October 2015. A total of 25 products—19 biosimilars and 6 originators—were included in the analysis.
Overall, 142 safety concerns were retrieved from RMP data, corresponding to 55 safety concerns. Of these concerns, 22 (40%) were classified as having high clinical relevance, 21 (38%) as having medium clinical relevance, and 12 (22%) as having low clinical relevance.
The therapy for which the most differences in safety information were observed between the reference and its biosimilars was infliximab; of 14 general safety concerns for infliximab, 2 were noted in RMP data for the originator only, while 3 concerns—bowel obstruction, hematologic reactions, and lack of efficacy—were noted in RMP data for the biosimilars only.
A quantitative comparison for highly clinically relevant safety concerns showed that the RMP of the originator product listed 4 types of autoimmune events and 3 types of infections that were not listed for the biosimilars. Meanwhile, the biosimilars’ RMP data noted 3 types of neoplasms not noted for the originator. However, the authors point out, the safety concerns of the originator versus the biosimilar infliximab products shared the same origins, though they may have been specified differently; for example, “melanoma” was noted for the reference product, while “skin cancer” was noted for the biosimilars.
Biosimilar filgrastim products, too, had a notable difference from reference filgrastim; the biosimilar RMP data noted the safety concern of cytokine release syndrome (though capillary leak syndrome, which is considered linked to cytokine release syndrome, was noted for both originator and biosimilar filgrastim).
Biosimilar somatropin had new neoplasm, intracranial aneurysm, and intracranial hemorrhage reported as potential risks that were not shared by the originator, though this apparent discrepancy can be explained by the fact that the decision to present an RMP for the originator biologic is not publicly available.
The authors concluded that, based on available official information, no substantial differences were observed in the reporting of safety information for biosimilars and their originators. Some differences among infliximab products were observed, but, the authors say, infliximab also showed the most general safety concerns of all of the substances analyzed. The authors state that further post-marketing research is warranted for infliximab and its biosimilars, though the study’s analysis suggests similar safety outcomes among the infliximab products.