NEW YORK (Reuters Health)—Biosimilar tumor necrosis factor-alpha inhibitors appear equivalent to the branded original versions, according to a systematic review and meta-analysis.
As Dr. G. Caleb Alexander tells Reuters Health by email, “biologic treatments represent a rapidly growing proportion of prescription drug expenditures and thus there is enormous interest in whether or not biosimilar products are truly biosimilar.”
“Our results,” he adds, “suggest that, for this important class of drugs, the biosimilar versions appear to have the same safety and efficacy profiles as their branded counterparts (or as the originator products).”
In a paper online Aug. 1 in Annals of Internal Medicine, Dr. Alexander of Johns Hopkins Bloomberg School of Public Health in Baltimore and colleagues point out that there are five innovator TNF-alpha inhibitors on the U.S. market: adalimumab (Humira), certolizumab pegol (Cimzia), etanercept (Enbrel), golimumab (Simponi) and infliximab (Remicade).
In April 2016, they add, “the FDA approved the infliximab biosimilar, Inflectra, which is only the second biosimilar to receive market approval in the United States.”
The agent is already available in Canada, Australia, Korea and other countries. Other biosimilars are also available. For example, Korea has two approved etanercept biosimilars, and India currently has a handful of marketed biosimilars.
To investigate their performance, the team examined outcome in 19 studies. Eight were Phase I randomized trials, five were Phase III randomized trials and six were observational studies. Among participants were healthy volunteers, patients with inflammatory bowel disease, patients with ankylosing spondylitis and patients with rheumatoid arthritis.
Comparisons included CT-P13 vs. infliximab, SB4 and TuNEX vs. etanercept and ZRC-3197 vs. adalimumab.
The Phase I trials, say the researchers, showed that the pharmacokinetic parameters of the agents were within the prespecified equivalence margin.
The Phase III trials “suggested similar clinical responses and adverse events.” That was also the case in four cohort studies in patients who switched from infliximab to CT-P13, but cross-reactivity was seen in two studies.
Dr. Alexander concludes, “there has been considerable uncertainty as to whether biosimilar products are as safe and effective as their referent or originator, or branded counterparts, our results suggest that they at least in this case, are.”
In an accompanying editorial, Drs. Issam Zineh and Leah A. Christl of the U.S. Food and Drug Administration in Silver Spring, Md., note that, “In our experience, randomized, comparative, noninferiority studies of clinical outcomes alone are generally considered insufficiently sensitive to detect the impact of product differences between a proposed biosimilar and its reference product.”
Terminology is also important, they add, and the researchers “use the term ‘bioequivalence’ as a sort of all-encompassing comparability term.” It is easy, they add, “to conflate concepts of bioequivalence, biosimilarity, interchangeability, and therapeutic equivalence.”
Thus, they conclude, “We encourage further exploration of mechanisms to ensure common understanding of these concepts among the drug development, regulatory, clinical practice, patient, and payer communities.”