Available data from comparative clinical trials and observational studies strongly confirm the equivalence between CT-P13 and originator infliximab for the treatment of rheumatologic diseases.
A new review of studies analyzing the benefits and concerns of CT-P13, Celltrion’s infliximab biosimilar (marketed as Remsima and Inflectra) to Janssen’s originator drug Remicade, concludes that available data from comparative clinical trials and observational studies strongly confirm the equivalence between CT-P13 and originator infliximab for the treatment of rheumatologic diseases from both a pharmacodynamic (PD) and clinical point of view. Andrea Becciolini, MD, of the Department of Rheumatology at the University of Milan Gaetano Pini Institute, and coauthors said that their analysis of the literature, published in Drug Design, Development and Therapy, suggests interchangeability between originator infliximab and CT-P13 is a feasible and safe strategy to be applied in real-life clinical practice.
CT-P13 was approved in 2013, and was the first infliximab biosimilar approved by the European Medicines Agency (EMA) for marketing in the European Union (EU) for all the indications of the reference product. Inflectra was approved by the FDA in 2016. The EMA’s approval was granted based on a complete comparative research program that included 2 “crucial” randomized controlled trials: the PLANETAS (Program evaLuating the Autoimmune disease iNvEstigational Drug cT-p13 in Ankylosing Spondylitis [AS] patients) trial and the PLANETRA (Program evaLuating the Autoimmune disease iNvEstigational drug cT-p13 in Rheumatoid Arthritis [RA] patients) trial.
PLANETAS was a phase 1 trial comparing pharmacokinetics (PK), safety, and efficacy of innovator infliximab and CT-P13, each given as monotherapy infused intravenously in 250 patients with active AS. PLANETRA was a phase 3 trial comparing safety and efficacy of innovator infliximab and CT-P13, each administered intravenously in combination with methotrexate (MTX) in 606 patients with active RA who had inadequate responses to MTX.
Based on the results from these 2 trials and EMA approval, nearly all national EU drug agencies initially licensed CT-P13 for the treatment of treatment-naïve AS and RA patients. Later, by extrapolation, the EMA approved other indications granted to the originator infliximab. Subsequent extension studies of PLANETAS and PLANETRA that were published provided crucial data about the safety and efficacy of switching from innovator infliximab to CT-P13 in both AS and RA patients.
In addition, the authors note, recently published observational data from the NOR-SWITCH study and the DANBIO registry “represent the most important and comprehensive source of data on [CT-P13] today, and may be crucial for improving knowledge on efficacy and safety of a switching strategy.” However, the authors note that most regulatory agencies, including the EMA, require further post-marketing surveillance, and encourage the use of registries on biosimilars so that there is a detailed body of data on risks and safety concerns including immunogenicity and detection of any new safety problems.
Becciolini and coauthors conclude that long-term open-label extensions of comparative trials and the first real-life switching experiments for CT-P13 did not show unexpected differences in its efficacy or safety profile. Likewise, there were no unexpected differences in the immunogenicity of patients who switched from originator infliximab to CT-P13 compared with the group treated only with CT-P13. Although all these studies alone are not adequate to completely satisfy the new study design requirements proposed by the FDA concerning interchangeability, the favorable findings may be reassuring about single switches between originator infliximab and CT-P13. Taken together, the authors state, the findings “significantly affect the landscape of biosimilar regulatory pathways and strongly support CT-P13 introduction as a great opportunity for expanding the accessibility to these very effective and high-cost therapies.”