The efficacy and safety of eculizumab biosimilar in patients with paroxysmal nocturnal hemoglobinuria. Results of a phase III randomized open-label comparative clinical trial

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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.

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 Petersburg

Bulat 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, Ufa

Igor 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, Samara

Ilya 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, Barnaul

Tatiana 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, Ekaterinburg

Aleksandr 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, Chelyabinsk

Marina V. Kosinova

Belyaev Regional Clinical Hospital

Email: kulaginad@1spgmu.ru
ORCID iD: 0000-0001-9181-6184

зав. отд-нием гематологии ГАУЗ КОКБ

Russian Federation, Kemerovo

Vadim 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 Petersburg

Natalia 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, Kirov

Andrei V. Proidakov

Komi Republican Oncological Dispensary

Email: kulaginad@1spgmu.ru
ORCID iD: 0000-0002-5013-6614

зав. гематологическим отд-нием ГУ КРОД

Russian Federation, Syktyvkar

Vadim 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, Moscow

Yuri 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-Don

Yulia 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 Petersburg

Arina 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 Petersburg

Maria A. Morozova

BIOCAD

Email: kulaginad@1spgmu.ru
ORCID iD: 0000-0001-7755-7526

канд. мед. наук, мед. эксперт ЗАО «БИОКАД»

Russian Federation, Saint Petersburg

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Supplementary files

Supplementary Files
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2. Fig. 1. Distribution of patients by study groups.

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3. Fig. 2. Dynamics of the average values of the level of lactate dehydrogenase in the main period of the study.

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4. Fig. 3. Dynamics of the concentration of total eculizumab during the main study period.

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5. Fig. 4. Dynamics of hemolytic activity of blood serum complement (СН50) in patients during the main study period.

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6. Fig. 5. Dynamics of the level of C5-component of complement in blood serum of patients during the main period of the study.

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