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.

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.