Background Rheumatoid arthritis (RA) being a joint-destructive disease, patients with advanced stages of the disease face difficulties in operating conventional or pre-filled syringes (PFS) for subcutaneous (sc) administration. Therefore, GP2015, a proposed etanercept biosimilar, is planned to be presented in a ready to use, fixed dose, disposable autoinjector (AI), identical to secukinumab autoinjector, allowing one-hand injection without requiring fine finger manipulations.
Objectives To compare the pharmacokinetics (PK) and safety of GP2015 administered via AI or PFS in healthy male subjects.
Methods In this open-label, randomised, 2-way cross over study, male healthy subjects (N=51), ≥18–≤55 years of age, were randomised to receive a single 50 mg sc dose of GP2015 via AI or PFS followed by a wash-out period of at least 35 days and a second 50 mg sc injection of GP2015 via PFS or AI vice versa. Subsequent follow up was 28 days. Randomisation was stratified by body weight (50–79.9 kg, 80–99.9 kg, 100–140 kg), allocating 17 subjects per each weight category.
Results Out of 51 subjects enrolled into the study, 48 were evaluable for PK analysis. Subjects exhibited a mean body weight of 91.5 kg (range: 54.4–133.7 kg) and a mean body mass index (BMI) of 27.7 kg/m2 (range: 19.3–39.0 kg/m2). The 90% confidence intervals (CIs) for the ratios of geometric means of maximum observed serum concentration (Cmax), area under the serum concentration-time curve measured from the time of dosing to the last measurable concentration (AUC0-last), and AUC measured from the time of dosing and extrapolated to infinity (AUC0-inf) were contained within the limits of 80–125% confirming bioequivalence between GP2015 applied via AI or PFS (Table). Within each body weight category, the serum concentration profiles of GP2015 were similar for both treatment administrations. The 90% CI for the ratios of geometric means of all PK parameters were within 80–125% in low and medium weight groups. In the high weight group, due to a single subject with low exposure after dosing by PFS, the upper limit of the 90% CI was above 125%, while without this outlier the upper limit of CI was below 125%. The most common adverse events (AEs) regardless of relationship to the study drug were headache [GP2015-AI, n=8 (16%); GP2015-PFS, n=5 (10%)] and neutropenia [GP2015-AI, n=5 (10%); GP2015-PFS, n=5 (10%)]. All treatment related AEs were of mild severity and resolved during the study. None of the neutropenias (range: 1.1–1.7 x 109/L; reference range: 1.8–7.9 x 109/L) were considered clinically significant. No serious AEs or deaths occurred during the study. Three subjects had a mild injection site reaction [GP2015-AI, n=1 (2%); GP2015-PFS, n=2 (2%)]. No anti-drug antibodies were detected in any of the subjects.
Conclusions This study demonstrated PK bioequivalence of GP2015 administered by AI or PFS. Both administrations were bioequivalent, including when analysis was stratified by body weight. A single dose of 50 mg GP2015 administered by AI or PFS was well tolerated, with a safety profile consistent with previous reports for etanercept. These results suggest that the AI is an effective application form of GP2015 with a similar safety profile compared to the PFS.
Disclosure of Interest M. Afonso Employee of: Hexal AG, affiliate of Novartis, D. Kollins Employee of: Hexal AG, affiliate of Novartis, L. Macke Employee of: Hexal AG, affiliate of Novartis, H. Woehling Shareholder of: Hexal AG, affiliate of Novartis, Employee of: Hexal AG, affiliate of Novartis, G. Wuerth Employee of: Hexal AG, affiliate of Novartis