The erythropoiesis-stimulating agents (ESAs) are among the first biosimilars approved for use in Europe, a decade ago. As more real-world evidence accumulates on the comparable outcomes of several classes of biosimilars, support increases for their utilization abroad. This past week, researchers from Rome, using a real-time patient registry, have confirmed the safety and efficacy of biosimilar versions of erythropoiesis-stimulating agents (ESAs) compared with the originator product (epoetin-alpha).
Dr. Francesco Trotta, Department of Epidemiology, Lazio Regional Health Service, Rome, led a team of investigators who evaluated the use of ESAs in nearly 13,500 patients with chronic kidney disease or undergoing treatment for cancer in a region of Italy (total population, 6 million) over a 3-year period, assuming a 6-month course of the agents. They assessed all-cause mortality and need for blood transfusion and the incidence of major cardiovascular events and blood dyscrasia, which comprised a composite endpoint of effectiveness and safety.
The results of this study were published in BMJ Open. In comparing 3 ESA biosimilars (Abseamed®, Binocrit®, and Retacrit®) to the epoetin alpha originator drug (Eprex®), the researchers found that in patients with chronic kidney disease, the risk estimates for the effectiveness and safety measures were not significantly different. Using a composite outcome, the biosimilars demonstrated an adjusted hazard ratio of 1.02 compared with Eprex. The biosimilars were also compared with other ESAs, including darbapoetin alpha, epoetin beta, epoetin theta, and methoxypolyethyleneglycol-epoetin beta. Though not considered biosimilars to these agents, the epoetin alpha biosimilars recorded an adjusted hazard ratio of 1.09 compared with these other ESAs. For patients receiving oncology treatment, the biosimilars demonstrated a better hazard ratio for the all-cause mortality outcome (adjusted HR, 0.82), which was on the “margin of statistical significance.” In terms of the composite outcome, the biosimilars exhibited a slightly improved adjusted hazard ratio (0.91). Subgroup analysis revealed some minor differences in outcomes, but none that would alter a patient’s clinical approach.
The authors concluded, “In both settings, our findings are suggestive of no difference between biosimilars and originators on relevant effectiveness and safety outcomes measured during the follow-up period.”
These results should not be surprising based on the success (and proliferation) of the ESA class since 2007. The fact that a US version of epoetin alpha has not yet been approved is surprising: Pfizer’s Retacrit was submitted in 2014, with hopes of being the first biosimilar on the market, but a complete response letter from the FDA the following year short circuited this plan. No other epoetin biosimilar is on record as being filed for approval with the FDA at this time.