CT-P43 Shows Equivalent Efficacy, Safety for Plaque Psoriasis vs Ustekinumab

Kim Papp, MD, PhD
Credit: Arcutis Therapeutics

A phase 3 trial is shedding new light on the efficacy and safety of CT-P43, an ustekinumab biosimilar, in the management of moderate to severe plaque psoriasis in adult patients.

Results of the study, which included more than 500 patients, provide evidence of equivalent efficacy to originator ustekinumab, with comparable pharmacokinetic, safety, and immunogenicity profiles.¹

“This study demonstrated equivalence of the candidate ustekinumab biosimilar CT-P43 to originator ustekinumab with respect to efficacy, as determined by mean percent improvement from baseline in PASI score at week 12,” wrote investigators.¹

With initial approval for reference ustekinumab dating back more than a decade to the US Food and Drug Administration’s approval for moderate to severe plaque psoriasis in adult patients, ustekinumab has since received approval for indications ranging from plaque psoriasis in adults and pediatric patients to rheumatic and gastrointestinal diseases.^2,3 In the current study, investigators sought to examine the efficacy and safety of CT-P43, a candidate biosimilar, to reference ustekinumab for the treatment of moderate to severe plaque psoriasis.¹

To do so, a team of investigators led by Kim Papp, MD, PhD, president of Probity Medical Research Inc., launched a double-blind, randomized phase 3 trial comparing CT-P43 against ustekinumab in adult patients with moderate to severe plaque psoriasis from 34 centers in Estonia, Poland, Republic of Korea, and Ukraine. Per trial protocol, an initial screening period occurred from day 42 to day 1 and, following this period, patients were randomized in a 1:1 ratio to receive either CT-P43 or European Union-sourced originator ustekinumab for 16 weeks. For the purpose of analysis, patients were stratified by country, body weight, and prior use of biologic treatment for psoriasis at the first randomization. ¹

Following the initial 16-week treatment period, patients receiving originator ustekinumab were rerandomized in a 1:1 ratio to continue originator ustekinumab or switch to CT-P43, with those who were initially randomized to CT-P43 continuing to receive the biosimilar. This treatment period lasted from weeks 16 to 40.¹

For inclusion in the trial, patients needed to be aged 18 to 80 years of age and have plaque-type psoriasis diagnosed for 24 weeks or more prior to the first study drug administration. Investigators defined having plaque-type psoriasis as a Psoriasis Area and Severity Index (PASI) score of 12 or greater with an involved body surface area of 10% or greater and a static Physician’s Global Assessment score of 3 or greater.¹

The primary endpoint of interest was the mean percent improvement in PASI score at week 12. Investigators determined if equivalence was concluded if confidence intervals (CIs) for the estimate of treatment difference were within pre-defined equivalence margins. These predefined margins were 10% using the FDA approach or 15% using the European Medicines Agency (EMA) approach.¹

A total of 509 underwent randomization in the first treatment period. The 256-patient cohort randomized to CT-P43 had a median age of 41.0 (range, 18 to 74) years at baseline, 62.9% were male, and 90.2% were White. The 253-patient cohort randomized to originator ustekinumab had a median age of 41 (range, 18 to 77) years at baseline, 68.4% were male, and 90.9% were White.¹

Upon analysis, mean percent improvements in PASI score at week 12 were 77.93% for the CT-P43 cohort and 75.89% for the originator ustekinumab cohort using the FDA approach. Using the EMA approach, the corresponding values were 78.26% and 77.33%, respectively. Further analysis suggested the estimated treatment differences were 2.05 (90% CI, -0.23 to 4.32) and 0.94 (95% CI, -2.29 to 4.16), with investigators noting equivalence was achieved for both sets of assumptions. Investigators also highlighted additional efficacy parameters and pharmacokinetic, safety, and immunogenicity outcomes were comparable between treatment groups, including after switching from originator ustekinumab to CT-P43.¹

“This study demonstrated the equivalence in terms of efficacy of CT-P43 and originator ustekinumab in patients with moderate to severe plaque psoriasis. The [pharmacokinetic], safety and immunogenicity profiles of CT-P43 and originator ustekinumab were comparable,” investigators added.¹

References:

1. Papp KA, Lebwohl MG, Thaçi D, et al. 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. BioDrugs. Published online November 22, 2023. doi:10.1007/s40259-023-00630-5
2. Stelara TM (ustekinumab) receives FDA approval for treatment of moderate to severe plaque psoriasis with four-times-a-year maintenance dosing. Johnson & Johnson. September 25, 2009. Accessed November 29, 2023. https://johnsonandjohnson.gcs-web.com/news-releases/news-release-details/stelara-tm-ustekinumab-receives-fda-approval-treatment-moderate.
3. Stelara (ustekinumab) FDA approval history. Drugs.com. January 28, 2021. Accessed November 29, 2023. https://www.drugs.com/history/stelara.html.