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. 2018 Dec;5(2):403-421.
doi: 10.1007/s40744-018-0119-1. Epub 2018 Jun 29.

Similar Pharmacokinetics of the Adalimumab (Humira®) Biosimilar BI 695501 Whether Administered via Subcutaneous Autoinjector or Prefilled Syringe (VOLTAIRE®-AI and VOLTAIRE®-TAI): Phase 1, Randomized, Open-Label, Parallel-Group Trials

Steven Ramael  1 , Benjamin Van Hoorick  2 , Renger Tiessen  3 , Thijs van Iersel  3 , Viktoria Moschetti  4 , Benjamin Lang  5 , Ivo Sonderegger  4 , Sabrina Wiebe  5 , Bernd Liedert  4 , Girish Jayadeva  4
Affiliations

Similar Pharmacokinetics of the Adalimumab (Humira®) Biosimilar BI 695501 Whether Administered via Subcutaneous Autoinjector or Prefilled Syringe (VOLTAIRE®-AI and VOLTAIRE®-TAI): Phase 1, Randomized, Open-Label, Parallel-Group Trials

Steven Ramael et al. Rheumatol Ther. 2018 Dec.

Abstract

Introduction: BI 695501 has shown similar efficacy, safety, and immunogenicity to the adalimumab reference product, Humira®. We present two phase 1 studies comparing the pharmacokinetics, safety, and immunogenicity of BI 695501 delivered via autoinjector (AI) vs. prefilled syringe (PFS).

Methods: Both trials were randomized, open-label, parallel-group studies undertaken in subjects aged ≥ 18-65 years. VOLTAIRE®-AI (NCT02606903) recruited healthy, Caucasian, male, non-athletic volunteers with BMI ≥ 18 to ≤ 30 kg/m2. VOLTAIRE®-TAI (NCT02899338) recruited healthy men and women with BMI > 17.5 to < 35 kg/m2. In both studies, a single dose of BI 695501 40 mg was administered via AI or PFS to the abdomen (VOLTAIRE®-AI) or thigh (VOLTAIRE®-TAI). The observation period was 43/57 days and the safety follow-up was 70 days. Co-primary endpoints were AUC0-1032 or AUC0-1368, Cmax, and AUC0-∞. Safety and immunogenicity were assessed.

Results: Subjects (VOLTAIRE®-AI: N = 71; VOLTAIRE®-TAI: N = 162) were randomized to AI (n = 35; n = 81) or PFS (n = 36; n = 81). Baseline characteristics were balanced between treatment groups in each study. Total exposure of BI 695501 was similar for both groups; adjusted geometric mean ratios for AUC0-∞, AUC0-1032, and Cmax were 106.17, 104.09, and 114.83%, respectively, for VOLTAIRE®-AI; 103.19, 101.71 (AUC0-1368), and 100.11% for VOLTAIRE®-TAI. In both studies, similar immunogenicity was observed between groups in terms of frequency of binding and neutralizing anti-drug antibody-positive subjects. Incidence of adverse events was similar for both groups.

Conclusions: Pharmacokinetics and immunogenicity of BI 695501 delivered via AI were similar to administration using a PFS, independent of injection site. No differences are expected between AI and PFS use in clinical practice.

Funding: Boehringer Ingelheim.

Keywords: Adalimumab; Autoinjector; BI 695501; Biosimilar; Prefilled syringe.

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Figures

Fig. 1
Fig. 1
a AI and b PFS presentations. AI autoinjector, PFS prefilled syringe
Fig. 2
Fig. 2
Patient disposition in a VOLTAIRE®-AI and b VOLTAIRE®-TAI. AI autoinjector, EOT end of trial, PFS prefilled syringe. *Patients who did not complete the EOT visit could still complete the day 70 safety follow-up visit
Fig. 3
Fig. 3
Arithmetic mean plasma concentration–time profiles for BI 695501 administered via AI or PFS (± SD) in a VOLTAIRE®-AI and b VOLTAIRE®-TAI. AI autoinjector, PFS prefilled syringe, SD standard deviation
Fig. 4
Fig. 4
BMI vs. total exposure by method of administration (AI or PFS) (shown as log-transformed AUC0–∞, observed and Cmax) in a, b VOLTAIRE®-AI and c, d VOLTAIRE®-TAI. AI autoinjector, AUC0–∞, observed area under the plasma concentration–time curve from 0 extrapolated to infinity, based on observed concentrations at the last observation, BMI body mass index, Cmax maximum plasma concentration, Ln natural logarithm, PFS prefilled syringe
Fig. 4
Fig. 4
BMI vs. total exposure by method of administration (AI or PFS) (shown as log-transformed AUC0–∞, observed and Cmax) in a, b VOLTAIRE®-AI and c, d VOLTAIRE®-TAI. AI autoinjector, AUC0–∞, observed area under the plasma concentration–time curve from 0 extrapolated to infinity, based on observed concentrations at the last observation, BMI body mass index, Cmax maximum plasma concentration, Ln natural logarithm, PFS prefilled syringe
Fig. 5
Fig. 5
Proportions of patients who were i ADA-positive and ii nAb-positive in a VOLTAIRE®-AI and b VOLTAIRE®-TAI. ADA anti-drug antibody, AI autoinjector, nAb neutralizing antibody, PFS prefilled syringe
Fig. 6
Fig. 6
ADA titers for ADA-positive subjects over time in a VOLTAIRE®-AI and b VOLTAIRE®-TAI. Box and whisker plots indicating the median (line) within the 25% and 75% percentile box, arithmetic mean (diamond) and outliers (circles), and 10% and 90% percentile for whiskers. ADA anti-drug antibody, AI autoinjector, nAb neutralizing antibody, PFS prefilled syringe
See this image and copyright information in PMC

References

    1. AbbVie Inc. Humira® US prescribing information October 2017. https://www.rxabbvie.com/pdf/humira.pdf. Accessed Jan 2018.
    1. Boehringer Ingelheim International Gmbh. Cyltezo® US prescribing information August 2017 [cited January 2018].
    1. Boehringer Ingelheim International Gmbh. Cyltezo® Summary of product characteristics November 2017 [cited January 2018].
    1. Wynne C, Altendorfer M, Sonderegger I, Gheyle L, Ellis-Pegler R, Buschke S, et al. Bioequivalence, safety and immunogenicity of BI 695501, an adalimumab biosimilar candidate, compared with the reference biologic in a randomized, double-blind, active comparator phase I clinical study (VOLTAIRE®-PK) in healthy subjects. Expert Opin Investig Drugs. 2016;25:1361–1370. doi: 10.1080/13543784.2016.1255724. - DOI - PubMed
    1. Cohen SB, Alonso-Ruiz A, Klimiuk PA, Lee EC, Peter N, Sonderegger I, et al. Similar efficacy, safety and immunogenicity of adalimumab biosimilar BI 695501 and Humira reference product in patients with moderately to severely active rheumatoid arthritis: results from the phase III randomised VOLTAIRE-RA equivalence study. Ann Rheum Dis. 2018;77(6):914–921. - PMC - PubMed