Long-term data on the proposed adalimumab biosimilar BCD-057 in patients with moderate to severe psoriasis: A randomized controlled trial

Alexey V Samtsov, Andrey L Bakulev, Vladislav R Khairutdinov, Muza M Kokhan, Tat'yana V Korotaeva, Iskander K Minullin, Olga A Vylegzhanina, Valery V Dubenskiy, Bulat V Khalilov, Alkes A Khotko, Olga S Zykova, Irina V Chumachenko, Alexander M Lukyanov, Antonina V Artemeva, Polina P Pukhtinskaia, Alexey V Samtsov, Andrey L Bakulev, Vladislav R Khairutdinov, Muza M Kokhan, Tat'yana V Korotaeva, Iskander K Minullin, Olga A Vylegzhanina, Valery V Dubenskiy, Bulat V Khalilov, Alkes A Khotko, Olga S Zykova, Irina V Chumachenko, Alexander M Lukyanov, Antonina V Artemeva, Polina P Pukhtinskaia

Abstract

Introduction: The objective of this study was to demonstrate that BCD-057 is similar to innovator adalimumab (iADA) in terms of efficacy, safety, and pharmacokinetics in steady state in the target population of patients with moderate to severe plaque psoriasis (NCT02762955).

Methods: Patients were randomized in 1:1 ratio to receive 80 mg of BCD-057 or iADA at week 0 and 40 mg thereafter every other week from week 1. At week 24 patients from iADA group were re-randomized (1:1) to continue iADA or to be switched to BCD-057. The primary efficacy endpoint was 75% improvement in Psoriasis Area and Severity Index from baseline (PASI 75), secondary endpoints included PASI percent improvement and relative change in affected Body Surface Area (BSA) from baseline at weeks 16, 24, 33, and 55. Safety was assessed through monitoring of adverse events (AEs) and antidrug antibodies. Pharmacokinetics was evaluated at steady state.

Results: Overall, 346 adult patients were included in the study (174/172 patients in BCD-057/iADA arms, respectively). At week 16 PASI 75 was achieved by 60.34% and 63.37% of patients in BCD-057 and iADA arms, respectively (p = 0.5622). Bounds of the calculated 95% confidence interval (CI) for the difference between PASI 75 responses in arms [-13.26%; 7.2%] fall within the equivalence margin [-15% to 15%] demonstrating equivalent efficacy of BCD-057 and iADA. At week 55 81.61%, 85.56%, and 80.49% of patients in BCD-057, iADA and iADA/BCD-057 arms achieved PASI 75. Comparison of the secondary endpoints did not show significant differences between arms. A comparable pharmacokinetics was shown at steady state. Safety profiles and proportions of patients with antidrug antibodies were similar between arms. The switch from the iADA to BCD-057 did not affect the immunogenicity profile.

Conclusion: Obtained data demonstrate that BCD-057 and iADA are highly similar in clinical efficacy, pharmacokinetics, safety, and immunogenicity in patients with moderate to severe plaque psoriasis.

Conflict of interest statement

The study was sponsored and designed by JSC BIOCAD. AVA and PPP are employees of JSC BIOCAD. Other authors declare receiving research support from JSC BIOCAD as the site investigators for BCD-057-2 study. The site investigators collected the data, JSC BIOCAD conducted the data analyses, and all the authors had access to the data. All the authors vouch for the completeness and accuracy of the data and analyses for their respective studies and vouch for the fidelity of this report to the study protocol. Agreements between JSC BIOCAD and the investigators included provisions relating to confidentiality of the study data. The initial draft of the manuscript was written by clinical research scientists, with subsequent revisions by all the authors. All the authors made the decision to submit the manuscript for publication. Additional conflicts of interest are described below. This commercial affiliation does not alter our adherence to PLOS ONE policies on sharing data and materials. AVS has received grant/research support from: Novartis, Eli Lilly, Johnson&Johnson, Celgene, Glenmark, Galderma, Sanofi. ALB has received grant/research support from: AbbVie, Eli Lilly, Pfizer, UCB, MSD, Novartis, Galderma, Celgene, Leo Pharma and Johnson&Johnson, served as a consultant for: Novartis, Celgene and Johnson&Johnson, and received speaker’s bureau fees from: AbbVie, Eli Lilly, Galderma, UCB, Novartis, Celgene and Johnson&Johnson. VRKh served as a scientific consultant and has received grant/research support from: Akrikhin, Alkoy, Belupo, Bosnaliejk, Verteks, Glenmark, Elfa, Leo Pharma, MSD, Novartis, Pfizer, Sun Pharma, Sanofi, Celgene, Pharmtec, AbbVie, Eli Lilly, Jadran, Janssen. MMK has received grant/research support from: AbbVie, Eli Lilly, Pfizer, UCB, MSD, Novartis, Galderma, Celgene, Leo Pharma and Johnson&Johnson, served as a consultant for: Novartis, Celgene and Johnson&Johnson, and received speaker’s bureau fees from: AbbVie, Eli Lilly, Galderma, UCB, Novartis, Celgene and Johnson&Johnson. TVK has received grant/research support/speaker’s bureau fees from: AbbVie, Pfizer, UCB, Novartis, Janssen, Eli Lilly, BMS. OAV has received grant/research support from: AbbVie, Novartis, Merck. BVKh has received grant/research support from: Merck, Regeneron, Boehringer Ingelheim, Leo Pharma.

Figures

Fig 1. The CONSORT flow diagram.
Fig 1. The CONSORT flow diagram.
Fig 2. Study design.
Fig 2. Study design.
Fig 3. PASI percent improvement from baseline.
Fig 3. PASI percent improvement from baseline.
Fig 4. PASI 75 response rate.
Fig 4. PASI 75 response rate.
(A) PASI 75 at week 16. (B) PASI 75 at week 24. (C) PASI 75 at week 33. (D) PASI 75 at week 55.
Fig 5. Changes from baseline in affected…
Fig 5. Changes from baseline in affected BSA (%).
Fig 6. Adalimumab concentrations (ng/mL) after multiple…
Fig 6. Adalimumab concentrations (ng/mL) after multiple administration of BCD-057 or iADA.

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