P0879 The totality of evidence for FYB202 – an EU-approved and US-licensed biosimilar to reference ustekinumab
Authors: Balser S , Freudensprung B , Huebner K , Moreau I , Nopora K , Pippig S , Schmid M , Trieb M , Wolschin F 
Published: January 2025

Abstract

Background
Ustekinumab is a fully human IgG1/kappa monoclonal antibody to interleukin (IL)-12/23. It is authorized for the treatment of moderate to severe plaque psoriasis, active psoriatic arthritis, and active inflammatory bowel disorder. FYB202 has been approved by both EMA and FDA in September 2024 as a biosimilar to reference ustekinumab based on extensive comparative analytical characterization data and the proof of equivalence in clinical performance.

Methods
A full set of critical quality attributes was investigated with a comprehensive set of analytical methods. Functional comparability of FYB202 to the reference product for the main mechanism of action was assessed with IL-12 and IL-23 binding and bioassays. Equivalence in PK and efficacy as well as similarity in safety, tolerability, and immunogenicity were evaluated in clinical trials in healthy subjects and psoriasis patients.

Results
FYB202 was found to be analytically similar to reference ustekinumab with respect to physicochemical and biological properties, including structure, function, purity, and potency. Most relevant potency results are shown in Figure 1. A 3-arm PK study in 491 healthy volunteers demonstrated PK equivalence between FYB202 and both EU-approved and US-licensed ustekinumab and between the two reference drugs (all 90% CIs were within the predefined equivalence margin of 80 to 125% (Balser1). FYB202 was shown to be equivalent to reference ustekinumab in 392 patients with moderate-to-severe plaque psoriasis, with the mean percent improvement in PASI score from baseline to week 12 within the predefined equivalence intervals for both the EU- and US-specific analyses. The similarity in response was maintained over the whole course of the study. Transitioning from reference product to FYB202 had no clinically relevant effect on efficacy, safety, or immunogenicity (Papp2).

Conclusion
FYB202 has been shown to have similar physicochemical and functional properties and equivalent clinical performance was shown in clinical studies. Based on a totality of evidence approach, proof of therapeutic equivalence in the sensitive psoriasis population allows for extrapolation to other indications, with similar clinical performance of FYB202 and reference ustekinumab assumed across all approved indications. FYB202 provides a safe and effective biosimilar alternative for patients in need of ustekinumab therapy.

References
1.Balser, S., Nopora, K., Körner, J., Wedemeyer, R.-S., Anschütz, M. and Schug, B. (2024), New Ustekinumab Biosimilar Candidate FYB202: Pharmacokinetic Equivalence Demonstrated in a Randomized, Double-Blind, Parallel-Group, Single-Dose Trial in Healthy Subjects. Clin Pharmacol Drug Dev.; https://doi.org/10.1002/cpdd.1473
2.Papp, K., Balser, S., Nopora, K., Freudensprung, B., Trieb, M. (2024), A randomised, double-blind trial to compare the efficacy, safety, and immunogenicity of the proposed biosimilar ustekinumab (FYB202) with reference ustekinumab in patients with moderate-to-severe plaque psoriasis. EADV 2024, Poster PO984