OR WAIT null SECS
All primary endpoints evaluating pharmacokinetics were achieved and immunogenicity and safety were comparable across treatment arms.
In healthy adults, a single dose of the European Union-approved reference tocilizumab (EU-tocilizumab) biosimilar candidate, CT-P47, was well tolerated and demonstrated pharmacokinetic equivalence, according to a study published in Expert Opinion on Investigational Drugs.1
Although biologics have revolutionized treatment for immune-mediated inflammatory disease over the last 2 decades, their high costs have hindered patient access. Biosimilars, however, are generally more cost effective compared with the reference product, can improve patient access, and can lead to further advancements in therapy. Biosimilars are defined as biologic products with no clinically meaningful differences compared with the reference drug including safety, efficacy, and immunogenicity.2
“At present, no biosimilars of tocilizumab have obtained regulatory approval from the US Food and Drug Administration (FDA) or European Medicines Agency (EMA), although results of phase 1 studies comparing intravenous- or subcutaneous-administered candidate tocilizumab biosimilars with the reference product have been published,” wrote a group of Korean investigators. “CT-P47 is among the candidate tocilizumab biosimilars currently in clinical development, for administration by subcutaneous or intravenous routes.”
A double-blind, multicenter, parallel-group trial assessed a single (162 mg/.9 mL) subcutaneous dose of either CT-P47 or EU-tocilizumab in a randomized cohort of healthy adults. The primary endpoint was pharmacokinetic equivalence, defined as drug absorption, metabolism, distribution, and excretion by the body, based on area under the concentration – time curve (AUC) from time 0 to the last quantifiable concentration (AUC0–last), AUC from time 0 to infinity (AUC0–inf), and maximum serum concentration (Cmax). Equivalence was achieved if 90% confidence intervals (CIs) for the ratios of geometric least-squares means (gLSMs) fell between the 80%-125% equivalence margin. Other endpoints, including immunogenicity, safety, and additional pharmacokinetic endpoints, were also assessed.
Eligible patients were adults (aged 19 – 55 years) who were healthy, as confirmed by clinical laboratory tests, a full physical examination, and a detailed assessment of their medical history. They were also required to have a body mass index (BMI) between 18.5 and 28.0 kg/m2.
In the second part of the study, 289 Asian patients were randomized to receive either CT-P47 (n = 146) or EU-tocilizumab (n = 143). At baseline screening, 76.1% of participants were male and the median BMI was 23.85 kg/m2 in the CT-P47 cohort and 24.00 kg/m2 in the EU-tocilizumab group.
At day 43, all 3 primary endpoints were achieved and the 90% CIs for the ratios of gLSMs were within the equivalence margin. Immunogenicity and safety, as well as secondary pharmacokinetic endpoints, were comparable across treatment arms. Comparable proportions of patients had ≥1 positive post-baseline anti-drug antibodies (ADA) results in the biosimilar and reference product groups (13.9% vs 20.7%, respectively). A total of 237 treatment-emergent adverse events were reported in 55 (38.2%) patients receiving CT-P47 and 72 (51.4%) of patients in the EU-tocilizumab cohort, although most TEAEs were rated as grade 1 or 2 in intensity.
Investigators noted that including the 43-day sampling period strengthened the study by allowing the pharmacokinetic variables to be sufficiently described. However, as most patients were male and all were of Asian ethnicity, the generalizability of the findings may have been limited. To attempt to account for this, investigators randomized patients stratified by sex. Further, as most patients included in the study were relatively young (median age 26 years), future research focused on enrolling more diverse populations may enhance the generalizability and further confirm these findings.
“Following the demonstration of pharmacokinetic equivalence between CT-P47 and EU-tocilizumab and the comparability of immunogenicity and safety in this study, a phase 3 clinical trial is underway,” investigators concluded. “This will compare the efficacy and safety of intravenous-administered CT-P47 and EU-tocilizumab in patients with moderate-to-severe active rheumatoid arthritis.”