Background and Objectives YLB113 is being developed as a biosimilar of the antitumor necrosis factor-alpha antagonist etanercept, which is approved for the treatment of moderate-to-severe rheumatoid arthritis (RA) and other chronic immunemediated inflammatory diseases. An open-label, crossover, pharmacokinetic study was conducted to compare the relative bioavailability and safety of YLB113 and the etanercept reference product (RP) Enbrel ®. Methods Healthy male subjects aged 18-50 years were randomized to receive a single subcutaneous dose of YLB113 in one period and the etanercept RP in another period. A washout period of 28 days separated the two treatment periods. Blood samples were collected for pharmacokinetic analysis predose and until 480 h postdose during both periods. Results Overall, 52 subjects were enrolled, including 51 subjects who completed the first period and 43 subjects who completed the second period. The 90% confidence intervals for the least squares means derived from an analysis of the logtransformed pharmacokinetic parameters maximum serum concentration (C max), area under the serum concentration-time curve (AUC) from 0 to the last measurable concentration (AUC (0-t)) and AUC from 0 to infinity (AUC (0-∞)) for etanercept were between the limits of 80 and 125%. Thus, YLB113 met the bioequivalence criterion. YLB113 and the etanercept RP were well tolerated, with 24 subjects reporting 53 adverse events, including 42 mild and 11 moderate events. Treatmentemergent adverse events were reported by 14 and 16 subjects following the administration of YLB113 and the etanercept RP, respectively. Conclusions A single dose of YLB113 exhibited pharmacokinetic and safety profiles comparable with those of the etanercept RP in healthy adult male subjects. Therefore, YLB113 and the etanercept RP can be considered bioequivalent. These findings support the continued development of YLB113 for use in patients with RA. Jordan Food & Drug Administration unique trial number 31/Clinical/2018.

Aim This study aimed to demonstrate biosimilarity between Lupin’s Pegfilgrastim versus Neulasta with respect to pharmacokinetic (PK), pharmacodynamic (PD), immunogenicity, and safety profiles. Methods This double-blind, randomised, single-dose, two-sequence, two-treatment, two-period, crossover, comparative PK and PD study enrolled healthy subjects aged 18 to 45 years. The test product was Lupin’s Pegfilgrastim and the reference product was U.S.-licensed Neulasta. Blood samples were collected at different time points for assessment of PK, PD, and immunogenicity. Primary objectives included comparing the relative bioavailability and the pharmacodynamic effect of the two products. Secondary objectives included assessing immunogenicity, safety and tolerability. Biosimilarity was concluded if the 90% confidence interval (CI) of the ratio of the geometric least-squares mean (LSM) for PK and PD parameters were within 80 to 125%. Results The geometric mean ratios of Lupin’s Pegfilgrastim and Neulasta for primary PK parameters were C [94.37 (89.53 to 99.47%)], AUC [94.76 (89.83 to 99.95%)] and AUC [94.82 (89.90 to 100.02%)], and for primary PD parameters were ANC_C [100.59 (98.96-102.25%)] and ANC_AUEC [100.51 (99.18,101.85%)]. The corresponding 90% CIs were within the pre-defined equivalence limit of 80% and 125%. The incidence of ADA formation was similar between patients receiving Lupin’s Pegfilgrastim and Neulasta. No new safety concerns were observed. Conclusion This study establishes biosimilarity of Lupin’s Pegfilgrastim and Neulasta with respect to PK and PD profiles. No clinically meaningful differences were observed between the biosimilar and the reference product in terms of immunogenicity, safety, and tolerability profiles.