Background/Purpose: ONS-3010 is being developed as a biosimilar candidate of Humira^® (Adalimumab), a full-length recombinant human IgG1 monoclonal antibody specific for TNFα. This study evaluated the bioequivalence (BE) of single-dose pharmacokinetics (PK), safety and tolerability of ONS-3010 with specific assessment of immunogenicity compared to EU Humira^® and US Humira^®.

Methods: One hundred and ninety-eight (198) healthy male/female subjects (66 subjects per treatment group, gender balanced), were randomized to this double blind, single-dose study. The study duration was 14 weeks (screening: 4 weeks; PK/safety: 10 weeks). The subjects received a subcutaneous dose of 40 mg with either ONS‑3010 or Humira^® (EU or US product). PK and immunogenicity blood samples were collected at regular intervals. BE was assessed using general linear model procedures in SAS^®, ANOVA on ln-transformed AUC_0‑∞, C_max (primary endpoints) and AUC_0-last. The ratio of geometric means with its 90% confidence intervals (CI), were calculated for AUC_0-last, AUC_0-∞, and C_max. Equivalence bounds of 80.00-125.00% were used (ratio of geometric means [ONS-3010/Humira]: AUC_0‑∞, AUC_0-last, C_max,). Adverse events (AEs) and serious AEs (SAEs) were monitored and recorded. Positive immunogenicity samples were investigated for specificity of binding.  

Results: The PK profiles for EU Humira^®, US Humira^® and ONS-3010 were similar in shape (Figure 1). On the primary endpoints, AUC_0-∞ and C_max, equivalence was demonstrated (i.e., ratio of geometric means ONS-3010/EU Humira^® 1.03 [CI: 0.94 – 1.20] and 1.00 [0.92 – 1.08], ONS-3010/US Humira^® 1.06 [0.94 – 1.20] and 1.06 [0.98 – 1.15], EU Humira^®/US Humira^® 1.04 [0.92 – 1.17] and 1.07 [0.99 – 1.15], for AUC_0‑∞ and C_max respectively). Equivalence was also demonstrated for the secondary PK endpoint, AUC_0-last. One SAE reported in the ONS-3010 treatment group led to hospitalization (bacterial abscess [Lymphadenitis colli]). AEs were evenly divided over treatments, usually mild in severity, and self-limiting (Table 1). Immunogenicity results showed similar profiles in the 3 treatment groups for anti-drug and neutralizing antibodies.     Figure 1 Concentration-Time Profiles         Table 1 Most Frequently Reported* Adverse Events

*Regardless of relationship    

Conclusion: The PK data for Humira^® and ONS-3010 showed similar profiles over time. Equivalence was demonstrated on the primary (AUC_0-∞ and C_max) and secondary (AUC_0-last) endpoints. There was no significant difference in immunogenicity or overall safety, except for a reduction in the burning sensation at the ONS-3010 injection site.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/a-randomized-double-blind-single-dose-study-to-assess-the-pharmacokinetics-safety-and-tolerability-of-ons-3010-adalimumab-oncobiologics-inc-compared-to-two-reference-products-of-humira/