Samsung Bioepis’ Ustekinumab Biosimilar Demonstrates PK Equivalence in Healthy Adults

A phase 2 study demonstrated pharmacokinetic (PK) bioequivalence of the proposed ustekinumab biosimilar SB17 (Samsung Bioepis) to the EU- and US-sourced reference products. The authors also reported safety, tolerability, and immunogenicity were “comparable” between the 3 groups.

Ustekinumab is a monoclonal antibody targeting the p40 subunit of interleukin (IL)-12 and IL-23, cytokines involved in the pathogenesis of several inflammatory diseases. Ustekinumab blunts the inflammatory response by blocking the interaction of IL-12 and IL-23 with a receptor on the surface of natural killer cells and T cells.

The reference product (Stelara) was originally approved to treat moderate to severe plaque psoriasis in the US and European Union (EU) in 2009, and is now approved for several other chronic inflammatory diseases.

Previous analytical and non-clinical studies have established structural, physicochemical, and biological similarity to the reference product, and the current study aimed to compare PK parameters, safety, tolerability, and immunogenicity between SB17 and both the US and EU-sourced reference products in healthy adults.

A total of 201 participants were randomized to receive a single subcutaneous dose of 45 mg of the biosimilar, US reference ustekinumab, and EU reference ustekinumab. The primary PK end points were the area under the concentration-time curve from time zero to infinity (AUC_inf) and maximum serum concentration (C_max). Baseline characteristics of the participants in the 3 groups were “generally comparable,” the authors said, except for body weight which was significantly different between groups.

Primary Pharmacokinetic Endpoints Within Equivalence Margins

The authors noted that each pair of mean serum concentration-time profiles was “superimposable and comparable.” The ratios of geometric least-squares means AUC_inf and C_max were 0.99 and 0.90 for SB17 compared to the EU reference product, 1.01 and 0.94 for SB17 compared to the US reference product, and 1.02 and 1.05 for the EU compared to the US reference product. All 90% CIs for the ratios of AUCinf and Cmax between groups were within the predefined bioequivalence margin of 0.8-1.25.

Since body weight differed between groups, body-weight adjusted analyses were also carried out, and all 90% CIs were within the equivalence margins and contained 1.0. The authors added that all secondary pharmacokinetic endpoints were comparable across the 3 treatment groups.

Safety and Immunogenicity

Rates of treatment-emergent adverse events (TEAEs) were “comparable,” at 69%, 58%, and 66% in the SB17, EU reference, and US reference groups and no deaths or severe TEAEs were reported. The most common TEAE was headache.

There were no significant between-group differences in antidrug antibodies (ADAs) detected between groups, with 27%, 34%, and 34% of the participants receiving SB17, the EU reference product, and the US reference product positive for ADAs. Of participants positive for ADAs at the end of the study, approximately half (54%) were positive for neutralizing antibodies.

The authors concluded this phase 1 study demonstrates “equivalent pharmacokinetics and comparable immunogenicity, tolerability, and safety profiles” of SB17 and both EU and US reference products healthy adults, and said their results support conducting a phase 3 study of the candidate biosimilar in patients with psoriasis.

Reference

Jeong H, Kang T, Lee J, Im S. Comparison of SB17 and reference ustekinumab in healthy adults: A randomized, double-blind, single-dose, phase I study. Int J Clin Pharmacol Ther. 2024;62(5):231-240. doi:10.5414/CP204492