Differences in immunogenicity associated with non-product related variability: insights from two pharmacokinetic studies using GP2017, an adalimumab biosimilar

ABSTRACT

Introduction: Antidrug antibody (ADA) development is known to occur with adalimumab treatment and impacts adalimumab exposure. Here, we compare the impact of immunogenicity on pharmacokinetics (PK) across two randomized PK studies of GP2017, an approved biosimilar adalimumab, in healthy subjects.

Methods: Healthy male subjects (N= 107 in study GP17-104; N= 90 in study GP17-103) received a single 40 mg subcutaneous injection of the same GP2017 drug product batch. Cross-study PK comparison was performed for log-transformed C_max, AUC_0–360h, AUC_0–last, and AUC_0–inf, using an ANCOVA model.

Results: The proportion of ADA-positive subjects was higher in GP17-103 (in total 71.1%) vs. GP17-104 (57.9%). Comparison of GP2017 PK between studies showed that the exposure was lower in GP17-103 vs GP17-104, with 90% confidence intervals (CIs) for geometric mean ratios of AUC_0–last and AUC_0–inf being outside the range of 0.80–1.25. A subgroup analysis showed that in ADA-negative subjects 90% CIs for all PK parameters were within range, with geometric mean ratios close to 1.00.

Conclusion: The differences in GP2017 PK between the two groups are not considered to be product-related, but may be due to currently unknown factors related to differences between the two study populations.

KEYWORDS:

• Adalimumab
• biosimilar
• GP2017
• immunogenicity
• antidrug antibody
• PK similarity

Acknowledgments

Editorial support was provided by Jess Fox and Olga Ucar of Spirit, sponsored by Hexal AG/Sandoz. The authors are grateful to Dr. Martin Schiestl for careful revision and critical discussion of the manuscript.

Author contributions

All authors were involved in the conception and design of the study or in the analysis and interpretation of the data. All authors reviewed and revised the manuscript and provided their approval of the final version of the manuscript. All authors agree to be accountable for all aspects of the work.

Data availability

The authors confirm that the data supporting the findings of this study are available within the article and/or its supplemental materials.

Declaration of interest

In accordance with Taylor & Francis policy and our ethical obligation as researchers, we are reporting that we received funding from a company that may be affected by the research reported in the enclosed paper. We have disclosed those interests fully to Taylor & Francis.

Oliver von Richter, Lena Lemke, Halimuniyazi Haliduola, Alison Balfour, Britta Zehnpfennig, and Julia Jauch-Lembach are employees of Hexal AG/Sandoz. Andrej Skerjanec is an employee of Sandoz AG. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer Disclosures

One of the peer reviewers on this paper has acted as an advisor/consultant to Takeda, Celltrion, Janssen, Abbvie, GSK, and Ferring. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Supplemental material

supplemental date for this article can be accessed here.

Additional information

Funding

Studies GP17-103 and GP17-104 were sponsored by Hexal AG/Sandoz.