Results of a phase 3 noninferiority trial suggest that a biosimilar (Elizaria®) version of the agent eculizumab is not inferior in treatment of paroxysmal nocturnal hemoglobinuria (PNH), when compared with the eculizumab originator agent Soliris®, and the agents reportedly were similar in terms of safety. The results of this study were reported in the journal Annals of Hematology.
In the open-label ECU-PNH-III trial (ClinicalTrials.gov Identifier: NCT04463056), patients with PNH were randomized to either a group receiving the biosimilar, or to a group receiving the originator. Eculizumab in either group was administered according to whether a patient had prior exposure to eculizumab. A screening period lasted 4 weeks, treatment lasted 26 weeks, and the follow-up period was 2 weeks. The primary endpoint of the study was hemolysis activity based on analysis of the area under the lactate dehydrogenase (LDH) concentration-time curve while receiving eculizumab maintenance. Multiple other outcomes were also examined.
The biosimilar and originator groups each included 16 patients. Median ages were 39 years in the group receiving the biosimilar and 36.5 years in the group receiving the originator. Most patients (68.9%) in this study had previously received the originator agent.
In an analysis of the primary endpoint, mean LDH concentration-time curve results were found to be similar between groups. The mean LDH area under the curve value for the group receiving the biosimilar was 62,957.6 + 46,066.5 U/L*days (95% CI, 38,410.4 to 87,504.7). For the group given the originator, this value was 49,702.6 + 26,182.1 U/L*days (95% CI, 34,585.5 to 64,819.7; P =.351). The steady-state concentration of eculizumab 5 minutes prior to administration of either agent was a mean of 92.16 + 38.59 mg/mL with the biosimilar and 133.21 + 71.56 mg/mL with the originator.
Mean changes in hemoglobin levels during maintenance were considered comparable and were 2.4 + 14.3 g/L in the biosimilar group and 1.6 + 12.2 g/L in the originator group. During maintenance, stabilization of hemoglobin levels was seen in 37.5% of patients given the biosimilar and in 14.3% of patients given the originator. Rates of stabilization or increase in hemoglobin levels were 75.0% with the biosimilar and 64.3% with the originator.
Safety results were considered similar between the 2 agents. Adverse drug reactions were reported in 2 patients of the biosimilar group and in 3 patients of the originator group. Frequencies of identified antidrug antibodies were also reportedly not significantly different between groups.
“The assessment of the efficacy and safety of the Biosimilar showed no less efficacy and comparability in terms of safety with the Originator, which is necessary to confirm its biosimilarity to the original medicinal product,” the study investigators concluded in their report.
Disclosures: Some authors have declared affiliations with or received grant support from the pharmaceutical industry. Please refer to the original study for a full list of disclosures.
Kulagin AD, Ptushkin VV, Lukina EA, et al. Randomized multicenter noninferiority phase III clinical trial of the first biosimilar of eculizumab. Ann Hematol. 2021;100(11):2689-2698. doi:10.1007/s00277-021-04624-7