Tony Hagen is senior managing editor for The Center for Biosimilars®.
Separate studies including one on application methods for CT-P17 were reported at the American College of Rheumatology Convergence 2020 meeting.
A study of Celltrion’s CT-P17 adalimumab biosimilar candidate demonstrated pharmacokinetic (PK) and safety equivalence to US and EU samples of reference adalimumab1; and a separate study of difference administration methods for CT-P17 demonstrated equivalent outcomes2, in findings presented at American College of Rheumatology (ACR) Convergence 2020, the ACR’s virtual annual meeting.
Adalimumab reference product is indicated for arthritis, plaque psoriasis, ankylosing spondylitis, Crohn disease, and ulcerative colitis. CT-P17 was developed as a high concentration (100 mg/mL) citrate-free formulation of the reference product.
PK and Safety
PK and safety of CT-P17 relative to US- and EU-marketed reference adalimumab were evaluated in a healthy population (N = 312) randomized to a single dose in each of the 3 arms.
Investigators said the 90% CI intervals for each of the PK parameters were within the predefined equivalence margin of 80% to 125%; and secondary PK parameters were similar among the 3 treatment groups. Mean serum concentrations up to day 71 were comparable among the trial cohorts, they said.
Investigators also described a comparable safety profile among the 3 cohorts. Most treatment-emergent adverse events (TEAEs) were grade 1/2. The most frequent of these was injection site reaction, but no clinically notable differences were observed in lab results, vital signs, electrocardiogram results, or physical examinations among the patient groups.
With regard to immunogenicity, patients testing positive for antidrug antibodies (ADAs) and neutralizing ADAs were comparable in each cohort. In addition, each group followed a similar curve as numbers of patients testing positive increased over the study term.
Investigators concluded that PK equivalence of CT-P17 relative to high concentration (100 mg/mL), citrate-free formulations of the US- and EU-samples of reference product was demonstrated. Safety was also comparable, they said.
In a separate, phase 1 randomized, single-dose study in healthy participants comparing PK and safety of CT-P17 auto-injector (AI) and prefilled syringe (PFS) products, investigators observed comparable findings for mean peak and total drug exposure as well as for secondary PK parameters, safety, and immunogenicity.
The trial randomized enrollees 1:1 to 40 mg of CT-P17 AI (n = 98) or PFS (n = 95). Investigators said 92 patients completed treatment on AI and 83 completed treatment with PFS.
In both groups, mean peak and total systemic exposure were equivalent because the 90% CIs were within the predefined equivalence margin of 80% to 125%, investigators said. Maximum dose duration (Tmax) occurred at 132 hours for both treatment groups. Secondary PK parameters also were comparable between the AI and PFS groups, as were mean serum concentrations.
On safety, 60.2% and 51.7% of patients reported ≥ 1 TEAE in the AI and PFS groups, respectively. There were 2 TEAEs (grade 3), and all other TEAEs were grade 1/2. TEAEs considered related to CT-P17 were reported by 47 (50.5%) and 38 (43.7%) of patients in the AI and PFS groups, respectively. The most frequent were headache (11.8% and 9.2%) injection site reactions (8.6% and 6.9%).
1. Pharmacokinetics and safety of CT-P17, a proposed high concentration (100 mg/mL) adalimumab biosimilar, in comparison with EU-approved adalimumab and US-licensed adalimumab; results of a phase 1, randomized, double-blind, three-arm, single-dose study in healthy subjects. Yu KS, Jang I, Lim HS, et al. Presented at ACR Convergence 2020; November 5-9, 2020. Abstract 0204.
2. A phase 1, randomized, open-label, parallel group, single-dose study to compare the pharmacokinetics and safety of the auto-injector and pre-filled syringe of CT-P17, a proposed, higher concentration biosimilar (100 mg/mL) adalimumab, in healthy subjects. Keystone EC, Furst D, Kay J, et al. Presented at ACR Convergence 2020; November 5-9, 2020. Abstract 0199.