Efficacy and safety of biosimilar CT-P17 versus reference adalimumab in subjects with rheumatoid arthritis: 24-week results from a randomized study

Abstract

Background To demonstrate equivalent efficacy of the proposed high-concentration (100 mg/ml), citrate-free adalimumab biosimilar CT-P17 to European Union-approved adalimumab (EU-adalimumab) in subjects with active rheumatoid arthritis (RA). Methods This randomized, double-blind phase III study (ClinicalTrials.gov, NCT03789292) randomized (1:1) subjects with active RA at 52 centers to receive CT-P17 or EU-adalimumab 40 mg subcutaneously every 2 weeks until week 52. Results to week 24 are reported here. The primary endpoint was 20% improvement by American College of Rheumatology criteria (ACR20) response rate at week 24. Equivalence was concluded if the corresponding confidence intervals (CIs) for the estimate of treatment difference were within predefined equivalence margins: − 15 to 15% (95% CI; European Medicines Agency assumption); − 12 to 15% (90% CI; Food and Drug Administration assumption). Additional efficacy, pharmacokinetic, usability, safety, and immunogenicity endpoints were evaluated. Results 648 subjects were randomized (324 CT-P17; 324 EU-adalimumab). The ACR20 response rate at week 24 was 82.7% (n = 268/324) in both groups (intention-to-treat population). The 95% CI (− 5.94 to 5.94) and 90% CI (− 4.98 to 4.98) were within predefined equivalence margins for both assumptions and equivalent efficacy was concluded. Additional endpoints and overall safety were comparable between groups. Mean trough serum concentrations of CT-P17 were slightly higher than those of EU-adalimumab. Immunogenicity was slightly lower numerically for the CT-P17 group than for the EU-adalimumab group. Conclusions CT-P17 and EU-adalimumab have equivalent efficacy and comparable safety and immunogenicity in subjects with active RA. Overall safety of CT-P17 is consistent with the known safety profile of reference adalimumab. Trial registration ClinicalTrials.gov, NCT03789292. Registered 28 December 2018—retrospectively registered.

An Update Review of Biosimilars of Adalimumab in Psoriasis – Bioequivalence and Interchangeability

“…Patients receiving CT-P17 in period 1 continued CT-P17 treatment in period 2. The ACR20, ACR50 and ACR70 response rates at week 24 were 82.7%, 60.2% and 40.7% in the CT-P17 group and 82.7%, 63.6% and 44.4% in the EU-adalimumab group (95% CI −5.94 to 5.94), 38 which showed similar therapeutic efficacy between CT-P17 and EU-adalimumab.…”

“…37 Kay et al conducted a 52-week multicenter, randomized, double-blind, phase III clinical trial (N=648) to evaluate the efficacy of CT-P17 compared with EU-adalimumab and reported results up to week 24. 38 Moderate-tosevere RA patients were randomized to receive either CT-P17 or EU-adalimumab 40 mg injection every other week until week 24 (period 1). At week 26, patients receiving EU-adalimumab in period 1 were rerandomized either to transition to CT-P17 or to maintain EU-adalimumab treatment until 48 weeks (period 2).…”

Randomised, phase I pharmacokinetic study of adalimumab biosimilar CT‐P17 (40 mg/0.4 mL) by autoinjector and prefilled syringe in healthy subjects

“…Other studies in the CT‐P17 clinical development programme evaluated biosimilarity of CT‐P17 and reference adalimumab administered by PFS 14,15 . Patients with rheumatic disease have indicated a preference for AI over PFS administration of medications 16–20 ; therefore, the availability of an AI device option for CT‐P17 administration could benefit patients.…”

“…Other studies in the CT-P17 clinical development programme evaluated biosimilarity of CT-P17 and reference adalimumab administered by PFS. 14,15 Patients with rheumatic disease have indicated a preference for AI over PFS administration of medications [16][17][18][19][20] ; therefore, the availability of an AI device option for CT-P17 administration Limitations of this study include that it was not powered to formally assess safety, so there could be numerical differences in safety findings between groups that may not reflect true differences. Enrolment of both male and female subjects might increase variability in PK findings beyond that explained by differences in body weight, since drug PK profiles can differ between males and females, 37 including those reported for reference adalimumab.…”

“…10 However, despite FDA approval, no adalimumab biosimilar has yet been marketed in the USA due to patent disputes 11 CT-P17 is the first adalimumab biosimilar with a highconcentration formulation, approved by the EMA in February 2021 for the same indications as reference adalimumab. 2,[12][13][14][15] Aligned with the devices available for reference adalimumab self-administration, prefilled syringe (PFS) and autoinjector (AI) options are in development for CT-P17. 1,2 AI devices represent favourable treatment options for patients with rheumatic disease, who prefer AI over PFS administration.…”