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Clinical Trial
. 2021 Nov;100(11):2689-2698.
doi: 10.1007/s00277-021-04624-7. Epub 2021 Aug 16.

Randomized multicenter noninferiority phase III clinical trial of the first biosimilar of eculizumab

Alexander D Kulagin  1 , Vadim V Ptushkin  2 , Elena A Lukina  3 , Igor L Davydkin  4 , Alexander V Korobkin  5 , Vladimir S Shamrai  6 , Tatyana S Konstantinova  7 , Tatyana S Kaporskaya  8 , Tatyana A Mitina  9 , Tatyana I Ksenzova  10 , Evgeny V Zuev  11 , Oksana A Markova  11 , Elena V Gapchenko  11 , Dmitry A Kudlay  11   12
Affiliations
Clinical Trial

Randomized multicenter noninferiority phase III clinical trial of the first biosimilar of eculizumab

Alexander D Kulagin et al. Ann Hematol. 2021 Nov.

Abstract

Currently, eculizumab is the main effective treatment for paroxysmal nocturnal hemoglobinuria (PNH). The aim of this randomized multicenter noninferiority study was to evaluate the efficacy and safety of the Biosimilar (Elizaria) in comparison with the Originator (Soliris) in patients with PNH. Biosimilar and Originator were administered at a dose of 600 mg weekly for 4 weeks at the initial stage in naive patients, as well as for maintenance therapy at a dose of 900 mg every 2 weeks in all patients. The primary endpoint was a comparative assessment of hemolytic activity based on the area under the lactate dehydrogenase (LDH) concentration-time curve during the maintenance therapy. Thirty-two (32) patients were randomized for therapy with Biosimilar (n = 16) or Originator (n = 16). The mean values of LDH concentration-time curve were similar in both treatment groups without statistically significant differences (p > 0.05). Evaluation of secondary endpoints has shown no statistically significant differences between the groups. Safety values were comparable in both treatment groups. The data obtained confirm that the Biosimilar is not inferior to the Originator in terms of the main efficacy parameter, and is also comparable with it in terms of safety and additional efficacy parameters. Clinicaltrials.gov identifier: NCT04463056.

Keywords: Biosimilar; Eculizumab; Efficacy; Paroxysmal nocturnal hemoglobinuria; Safety.

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Conflict of interest statement

Kulagin A.: Alexion Pharmaceuticals, Inc: Consultancy, Research Funding (to Pavlov University); JSC GENERIUM: Consultancy, Honoraria, Research Funding (to Pavlov University). Ptushkin V.: Alexion Pharmaceuticals, Inc.: Consultancy, Research Funding; JSC GENERIUM: Research Funding; Janssen: Consultancy; AbbVie: Consultancy; Roche: Consultancy. Lukina E.: JSC GENERIUM: Research Funding; Sanofi Genzyme: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Other: Travel Reimbursement, Research Funding; Shire: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Other: Travel Reimbursement. Gapchenko E.: JSC GENERIUM: Employment. Markova O.: JSC GENERIUM: Employment. Zuev E.: JSC GENERIUM: Employment. Kudlay D.: JSC GENERIUM: Employment.

Figures

Fig. 1
Fig. 1
Distribution of patients in the study
Fig. 2
Fig. 2
Mean pharmacokinetic curves for the recorded eculizumab serum steady-state concentration in the extensive examination
Fig. 3
Fig. 3
Mean pharmacodynamic curves for the recorded membrane attack complex values (ng/mL) in steady state in the extensive PK study
Fig. 4
Fig. 4
Dynamics of lactate dehydrogenase activity during the study (95% CI for the mean)
Fig. 5
Fig. 5
The dynamics of the hemoglobin level during the study period (error bar shows 95% CI for the mean)
See this image and copyright information in PMC

References

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