New Ustekinumab Biosimilar Candidate FYB202: Pharmacokinetic Equivalence Demonstrated in a Randomized, Double-Blind, Parallel-Group, Single-Dose Trial in Healthy Subjects.

In the RUSTIC trial, pharmacokinetic (PK) similarity between the proposed ustekinumab biosimilar FYB202 and EU-approved (EU-Ref) and US-licensed ustekinumab (US-Ref) as well as between both reference drugs was assessed after a single 45-mg subcutaneous injection. Safety analyses comprised immunogenicity (antidrug antibodies, neutralizing antibodies), adverse events, and local tolerability. Overall, 491 healthy adults were randomized 1:1:1 and observed for up to 112 days; 486 completed the trial, and 478 were included in the PK analysis. All 3 comparisons showed PK similarity, since the 90% confidence intervals of the respective geometric mean ratios for area under the concentration-time curve from time 0 to infinity and maximum serum concentration were contained within the acceptance interval of 80%-125%. No clinically meaningful differences regarding overall safety, immunogenicity, and local tolerability were observed. Notably, after FYB202 administration, in fewer subjects at least 1 positive antidrug antibody result was observed compared to the reference groups (FYB202, 20%; EU-Ref, 42%; US-Ref, 51%). In conclusion, the RUSTIC trial demonstrated equivalent PK characteristics for FYB202 when compared to both EU-Ref and US-Ref ustekinumab and between both reference drugs. It provides the basis for the marketing authorization of FYB202, together with an extensive analytical characterization and the results of a confirmatory efficacy and safety trial in patients with moderate to severe plaque psoriasis.