Efficacy and safety of the ustekinumab biosimilar ABP 654 in patients with moderate-to-severe plaque psoriasis: a randomized, double-blinded, active-controlled, comparative clinical study over 52 weeks

Abstract Background ABP 654 is a biosimilar to ustekinumab reference product (RP). ABP 654 has been shown to have an amino acid sequence identical to ustekinumab RP and they are similar in structure, purity, and potency as well as clinical pharmacokinetics and safety in healthy volunteers. Objectives This randomized, double-blinded, active-controlled, single-transition, comparative clinical study (ClinicalTrials.gov ID NCT04607980) was conducted to compare the efficacy, safety, and immunogenicity of ABP 654 and ustekinumab RP in patients with moderate-to-severe plaque psoriasis. Methods Patients were randomized in a 1:1 ratio to receive ABP 654 or ustekinumab RP at a weight-based dose of 45 mg or 90 mg administered subcutaneously on day 1 (week 0), week 4, and week 16. At week 28, patients with a ≥75% improvement in Psoriasis Area and Severity Index (PASI) were re-randomized such that those initially randomized to ABP 654 continued to receive ABP 654 and those initially randomized to ustekinumab RP were re-randomized to either continue on ustekinumab RP or transition to ABP 654. The primary efficacy endpoint was PASI percent improvement from baseline to week 12. Secondary endpoints included additional efficacy measurements as well as an assessment of adverse events and antidrug antibodies. Results At week 12, the observed mean (SD) PASI percent improvement from baseline was 81.9 (19.9) and 81.9 (19.6) for the ABP 654 and ustekinumab RP treatment groups, respectively. The point estimate of the mean difference in PASI percent improvement from baseline to week 12 between the treatment groups was 0.14 with a 2-sided 90% confidence interval (CI) of (-2.6, 2.9), well within the prespecified similarity margin of (-10, +10). In addition, throughout the study, secondary efficacy analyses and safety and immunogenicity profiles were similar across the treatment groups. Conclusions These results indicate that ABP 654 and ustekinumab RP are clinically similar in efficacy, safety, and immunogenicity in patients with moderate-to-severe plaque psoriasis. Further, a single transition from ustekinumab RP to ABP 654 at week 28 had no impact on the efficacy, safety, or immunogenicity results for the remainder of the 52-week study, supporting a conclusion of no clinically meaningful differences between ABP 654 and ustekinumab RP.