The efficacy and safety of eculizumab biosimilar in patients with paroxysmal nocturnal hemoglobinuria. Results of a phase III randomized open-label comparative clinical trial
- Authors: Kulagin A.D.1, Bakirov B.A.2, Davydkin I.L.3, Elykomov I.V.4, Konstantinova T.S.5, Korobkin A.V.6, Kosinova M.V.7, Mazurov V.I.8, Minaeva N.V.9, Proidakov A.V.10, Ptushkin V.V.11, Shatokhin Y.V.12, Lin'kova Y.N.13, Zinkina-Orikhan A.V.13, Morozova M.A.13
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Affiliations:
- Pavlov First Saint Petersburg State Medical University
- Bashkir State Medical University
- Samara State Medical University
- Barnaul Regional Clinical Hospital
- Sverdlovsk Clinical Hospital №1
- Chelyabinsk Regional Clinical Hospital
- Belyaev Regional Clinical Hospital
- Mechnikov North-Western State Medical University
- Kirov Research Institute of Hematology and Blood Transfusion
- Komi Republican Oncological Dispensary
- Botkin City Clinical Hospital
- Rostov State Medical University
- BIOCAD
- Issue: Vol 93, No 11 (2021)
- Pages: 1340-1348
- Section: Original articles
- URL: https://journals.rcsi.science/0040-3660/article/view/99624
- DOI: https://doi.org/10.26442/00403660.2021.11.201226
- ID: 99624
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Abstract
Aim. To establish the equivalent efficacy and comparable safety profile of biosimilar Acveris and referent eculizumab product Soliris used for the treatment of paroxysmal nocturnal hemoglobinuria (PNH).
Materials and methods. Were included in the phase III multicenter 28 PNH patients, open-label clinical trial. Participants were randomized (1:1) into 2 treatment groups: investigational product (Acveris, n=14) and referent product (Soliris, n=14). Patients received eculizumab as the intravenous infusion 600 mg once a week during the first 4 weeks, 900 mg at week 5 and then 900 mg every 14 days (±2 days) up to week 27 of the study. The efficacy, pharmacokinetics, pharmacodynamics, safety and immunogenicity of the compared products were analyzed after the end of 27 weeks of the study. The primary efficacy endpoint was the area under the curve “LDH concentration–time” (AUCLDH) throughout the study period weeks 5–27.
Results. The difference between the mean AUCLDH values between the Acveris and Soliris groups was 5380.0 [-38 773.87; 49 533.87] U/l×days. The 95% CI limits for the difference in mean AUCLDH values between the groups fit the preset 95% CI [-146 500.9–146 500.9] U/l×days and establish the equivalent efficacy of the biosimilar and referent product according to the primary efficacy endpoint. The safety profile of both Acveris and Soliris was expected and comparable according to the proportion of patients with adverse events. The formation of binding antibodies to eculizumab was not detected in both the groups.
Conclusion. The study established the equivalent efficacy of biosimilar product Acveris and referent eculizumab product with the evidence of effective suppression of intravascular hemolysis in PNH patients along with a comparable favorable safety profile.
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##article.viewOnOriginalSite##About the authors
Aleksandr D. Kulagin
Pavlov First Saint Petersburg State Medical University
Author for correspondence.
Email: kulaginad@1spgmu.ru
ORCID iD: 0000-0002-9589-4136
д-р мед. наук, дир. НИИ детской онкологии, гематологии и трансплантологии им. Р.М. Горбачевой, зав. каф. гематологии, трансфузиологии и трансплантологии с курсом детской онкологии ФПО им. проф. Б.В. Афанасьева ФГБОУ ВО «Первый СПб ГМУ им. акад. И.П. Павлова»
Russian Federation, Saint PetersburgBulat A. Bakirov
Bashkir State Medical University
Email: kulaginad@1spgmu.ru
ORCID iD: 0000-0002-3297-1608
д-р мед. наук, доц., зав. каф. госпитальной терапии №2, врач-гематолог ФГБОУ ВО БГМУ
Russian Federation, UfaIgor L. Davydkin
Samara State Medical University
Email: kulaginad@1spgmu.ru
ORCID iD: 0000-0003-0645-7645
д-р мед. наук, проф., проректор по науч. работе, дир. НИИ гематологии, трансфузиологии и интенсивной терапии, зав. каф. госпитальной терапии с курсами поликлинической терапии и трансфузиологии ФГБОУ ВО СамГМУ
Russian Federation, SamaraIlya V. Elykomov
Barnaul Regional Clinical Hospital
Email: kulaginad@1spgmu.ru
ORCID iD: 0000-0002-0406-9828
канд. мед. наук, зав. гематологическим отд-нием КГБУЗ ККБ
Russian Federation, BarnaulTatiana S. Konstantinova
Sverdlovsk Clinical Hospital №1
Email: kulaginad@1spgmu.ru
ORCID iD: 0000-0003-4687-0784
канд. мед. наук, зав. отд-нием ГАУЗ СО СОКБ №1
Russian Federation, EkaterinburgAleksandr V. Korobkin
Chelyabinsk Regional Clinical Hospital
Email: kulaginad@1spgmu.ru
ORCID iD: 0000-0003-4922-3742
канд. мед. наук, зав. гематологическим отд-нием ГБУЗ ЧОКБ, гл. гематолог Минздрава Челябинской области
Russian Federation, ChelyabinskMarina V. Kosinova
Belyaev Regional Clinical Hospital
Email: kulaginad@1spgmu.ru
ORCID iD: 0000-0001-9181-6184
зав. отд-нием гематологии ГАУЗ КОКБ
Russian Federation, KemerovoVadim I. Mazurov
Mechnikov North-Western State Medical University
Email: kulaginad@1spgmu.ru
ORCID iD: 0000-0002-0797-2051
д-р мед. наук, проф., зав. каф., гл. науч. консультант ФГБОУ ВО «СЗГМУ им. И.И. Мечникова»
Russian Federation, Saint PetersburgNatalia V. Minaeva
Kirov Research Institute of Hematology and Blood Transfusion
Email: kulaginad@1spgmu.ru
ORCID iD: 0000-0002-8479-3217
канд. мед. наук, зам. дир. по лечебной работе ФГБУН КНИИГиПК
Russian Federation, KirovAndrei V. Proidakov
Komi Republican Oncological Dispensary
Email: kulaginad@1spgmu.ru
ORCID iD: 0000-0002-5013-6614
зав. гематологическим отд-нием ГУ КРОД
Russian Federation, SyktyvkarVadim V. Ptushkin
Botkin City Clinical Hospital
Email: kulaginad@1spgmu.ru
ORCID iD: 0000-0002-9368-6050
д-р мед. наук, зам. глав. врача по гематологии ГБУЗ «ГКБ им. С.П. Боткина»
Russian Federation, MoscowYuri V. Shatokhin
Rostov State Medical University
Email: kulaginad@1spgmu.ru
ORCID iD: 0000-0003-2246-2858
д-р мед. наук, проф., зав. каф. гематологии и трансфузиологии фак-та повышения квалификации и профессиональной переподготовки специалистов, зав. гематологическим отд-нием ФГБОУ ВО РостГМУ
Russian Federation, Rostov-on-DonYulia N. Lin'kova
BIOCAD
Email: kulaginad@1spgmu.ru
ORCID iD: 0000-0002-5463-1022
канд. мед. наук, дир. департамента клинической разработки ЗАО «БИОКАД»
Russian Federation, Saint PetersburgArina V. Zinkina-Orikhan
BIOCAD
Email: kulaginad@1spgmu.ru
ORCID iD: 0000-0002-8499-2232
рук. отд. клинической разработки «Аутоиммунные и орфанные заболевания» ЗАО «БИОКАД»
Russian Federation, Saint PetersburgMaria A. Morozova
BIOCAD
Email: kulaginad@1spgmu.ru
ORCID iD: 0000-0001-7755-7526
канд. мед. наук, мед. эксперт ЗАО «БИОКАД»
Russian Federation, Saint PetersburgReferences
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