Efficacy and Safety of Candidate Biosimilar CT-P43 Versus Originator Ustekinumab in Moderate to Severe Plaque Psoriasis: 28-Week Results of a Randomised, Active-Controlled, Double-Blind, Phase III Study

Abstract

Background: CT-P43 is a candidate ustekinumab biosimilar in clinical development.

Objectives: This paper aims to demonstrate equivalent efficacy of CT-P43 to originator ustekinumab in adults with moderate to severe plaque psoriasis.

Methods: This double-blind, phase III trial randomised patients (1:1) to receive subcutaneous CT-P43 or originator ustekinumab (45/90 mg for patients with baseline body weight ≤ 100 kg/> 100 kg) at week 0 and week 4 in Treatment Period I. Prior to week 16 dosing in Treatment Period II, patients receiving originator ustekinumab were re-randomised (1:1) to continue originator ustekinumab or switch to CT-P43; patients initially randomised to CT-P43 continued receiving CT-P43 (at weeks 16, 28 and 40). The primary endpoint of the trial was mean per cent improvement from baseline in Psoriasis Area Severity Index (PASI) score at week 12. Equivalence was concluded if confidence intervals (CIs) for the estimate of treatment difference were within pre-defined equivalence margins: ± 10% [90% CI; modified intent-to-treat set; Food and Drug Administration (FDA) approach] or ± 15% [95% CI; full analysis set for patients only receiving 45 mg doses in Treatment Period I; European Medicines Agency (EMA) approach]. Additional efficacy, pharmacokinetic, safety and immunogenicity endpoints were evaluated through week 52. Results to week 28 are reported here.

Results: In Treatment Period I, 509 patients were randomised (CT-P43: N = 256; originator ustekinumab: N = 253). The mean per cent improvement in PASI score at week12 was 77.93% and 75.89% for CT-P43 and originator ustekinumab, respectively (FDA approach); per the EMA approach, corresponding values were 78.26% and 77.33%. Estimated treatment differences were 2.05 (90% CI -0.23, 4.32) and 0.94 (95% CI -2.29, 4.16); equivalence was achieved for both sets of assumptions. Further efficacy parameters and pharmacokinetic, safety and immunogenicity outcomes were comparable between treatment groups, including after switching from originator ustekinumab to CT-P43.

Conclusions: CT-P43 demonstrated equivalent efficacy to originator ustekinumab in patients with moderate to severe plaque psoriasis, with comparable pharmacokinetic, safety and immunogenicity profiles.

Clinical trial registration: ClinicalTrials.gov Identifier: NCT04673786; date of registration: 17 December, 2020.

Fig. 1

Study design. ^aAt week 12, it was recommended that patients (in either group) who achieved at least PASI 50 continued study drug administration in Treatment Period II. ^bPrior to dosing at week 16, patients who were initially randomised to originator ustekinumab were re-randomised 1:1 to either continue receiving originator ustekinumab or to switch to CT-P43. ^cAt week 28, it was recommended that only patients who achieved at least PASI 75 continued further study drug administration (for all groups). ^dInvestigator-reported outcome assessments were performed by a qualified efficacy assessor per site. It was recommended that the same assessor perform the investigator-reported outcome assessments throughout the entire study period, if possible. EOS end of study, F/U follow-up, PASI 50/75 Psoriasis Area and Severity Index 50/75% improvement from baseline

Fig. 2

Patient disposition (ITT set). ^aThe second randomisation process was carried out at week 16. Patients randomised to the CT-P43 group for Treatment Period I continued to receive CT-P43 in Treatment Period II. Patients assigned to originator ustekinumab for Treatment Period I were randomised (1:1) to either continue originator ustekinumab or switch to CT-P43 in Treatment Period II. ITT, intent-to-treat

Fig. 3

Percentage improvement from baseline in PASI score (mITT set). mITT modified intent-to-treat, PASI Psoriasis Area and Severity Index, SD standard deviation