ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 1504

Pharmacokinetic Equivalence of ABP 501 Relative to Adalimumab: Results from a Randomized, Single-Blind, Single-Dose, Parallel Group Study in Healthy Subjects

Primal P. Kaur1, Vincent Chow2, Nan Zhang3, Mike Moxness4 and Richard Markus3, 1Amgen, Inc., Thousand Oaks, CA, 2Pharmacokinetics and Drug Metabolism, Amgen, Inc., Seattle, WA, 3Biosimilars, Amgen, Inc., Thousand Oaks, CA, 4Clinical Immunology and BSM, Amgen, Inc., Thousand Oaks, CA

Meeting: 2014 ACR/ARHP Annual Meeting

Keywords: ,

Session Information

Title: Rheumatoid Arthritis - Small Molecules, Biologics and Gene Therapy: Novel therapies, Biosimilars, Strategies and Mechanisms in Rheumatoid Arthritis

Session Type: Abstract Submissions (ACR)

Background/Purpose

Adalimumab is a recombinant IgG1 monoclonal antibody that binds to TNFα blocking its interaction with p55 and p75 cell surface receptors. ABP 501 is being developed as a biosimilar candidate to adalimumab; it contains a fully human recombinant monoclonal antibody with the same amino acid sequence. Evidence from analytical comparisons indicates that ABP 501 is highly similar to adalimumab. This report describes the pharmacokinetics (PK) results of ABP 501 compared with adalimumab sourced from the United States (US).

Methods

This was a single-blind, single-dose, parallel-group study in healthy male and female subjects, 18 to 45 years of age with a body mass index of 18 to 30 kg/m2. Subjects were randomized to receive 40-mg subcutaneous (SC) injection of ABP 501 or adalimumab. The primary objective was demonstration of PK equivalence of ABP 501 relative to adalimumab based on area under the serum concentration-time curve from time 0 extrapolated to infinity (AUCinf) and the maximum observed serum concentration (Cmax). Pre-specified equivalence criterion for the primary PK parameters was the standard 90% confidence interval (CI) for geometric means (GM) ratio to be within 0.80 to 1.25. Secondary endpoints included the safety, tolerability, and immunogenicity.

Results

Pharmacokinetics: A total of 67 subjects received ABP 501 and 69 subjects received adalimumab. Following a single dose, the adjusted least square (LS) GM of Cmax and AUCinf for ABP 501 were 3.22 µg/mL and 2140 µg.h/mL. The adjusted LS GM of Cmax and AUCinf for adalimumab were 3.11 µg/mL and 1920 µg.h/mL. Ratios of adjusted LS GM (90% CIs) between ABP 501 and adalimumab for Cmax and AUCinf were 1.04 (0.96, 1.12) and 1.11 (1.00, 1.24). The 90% CIs of these ratios were fully contained within 0.80 to 1.25 interval, confirming PK equivalence between ABP 501 and adalimumab.

Safety: There were no deaths, treatment-related serious adverse events, or treatment-related adverse events leading to discontinuation from the study. The most frequently reported treatment-related AEs included headache, nausea, nasopharyngitis, and oropharyngeal pain.

Immunogenicity: No pre-existing anti-drug antibodies (ADA) were detected at baseline. In the ABP 501 treatment group, 36 (54%) subjects developed binding antibodies and 12 (18%) developed neutralizing antibodies. In the adalimumab treatment group, 38 (55%) subjects developed binding antibodies and 15 (22%) developed neutralizing antibodies.

Conclusion

Results of this phase 1 study demonstrated PK equivalence of ABP 501 following a single 40-mg SC injection relative to that after a 40-mg SC injection of adalimumab sourced from the US. Similar ADA rates were observed in healthy subjects.

Disclosure:

P. P. Kaur,

Amgen,

1,

Amgen,

3;

V. Chow,

Amgen,

1,

Amgen,

3;

N. Zhang,

Amgen,

3,

Amgen,

3;

M. Moxness,

Amgen,

1,

Amgen,

3;

R. Markus,

Amgen,

1,

Amgen,

3.

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