韓國 Celltrion...世界第一學名藥抗體(Infliximab, CT-P13) 將於國際市場上市!!

Celltrion’s first biosimilar antibody is about to reach the market    JUNE 8, 2012 8:36 AM  Celltrion announced the results of its Remicade biosimilar, CT-P13 at the European League Against Rheumatism (EULAR) in Berlin, Germany.The Phase I trial was to compare the pharmacokinetic profile of CT-P13 with that of infliximab at steady state in terms of area under the concentration-time curve over a dosing interval and observed maximum serum concentration, and evaluate the efficacy and overall safety of both treatments in patients with Ankylosing Spondylitis (AS).  Two hundred fifty patients with active AS were randomized 1:1 to receive either CT-P13 or infliximab (5 mg/kg, 2-hour IV infusion per dose) at weeks 0, 2, and 6 (dose-loading phase) and at weeks 14, 22, and 30  (maintenance phase). Ratios of geometric means of primary PK parameters from the 2 treatment arms between weeks 22 and 30 were subjected to ANCOVA analysis at 90% confidence intervals. Efficacy measures (including ASAS20 and ASAS40), and safety parameters (including the incidence of adverse events) were also evaluated.  The mean (% CV) AUCT was 34855.45 (34.3%) µg-h/mL and 34688.71 (45.4%) µg-h/mL in the CT-P13 and infliximab arms, respectively. The mean (% CV) Cmax,ss was 153.52 (27.6%) µg/mL and 150.39 (26.9%) µg/mL in the CT-P13 and infliximab arms, respectively. The ratio (%) between the geometric means of the AUCT and Cmax,ss values in the CT-P13 and infliximab arms were 104.1% and 101.5%, respectively, between weeks 22 and 30, indicating PK equivalence in terms of AUCT and Cmax,ss.  Secondary parameters at week 30 were also comparable, including ASAS20 and ASAS40 response rates (70.5% for CT-P13 vs 72.4% for infliximab and 51.8% vs 47.4%, respectively). Adverse events considered by the investigators to be related to study treatment were reported in 57 (44.5%) patients and 58 (47.5%) patients in the CT-P13 and infliximab arms, respectively. Related adverse events due to infection were reported for 24/128 (18.8%) patients and 22/122 (18.0%) patients in the CT-P13 and infliximab treatment groups, respectively. Adverse events due to infusion reactions considered related to study drug were reported in 5 patients in the CT-P13 arm, and 6 patients in the infliximab arm. Tuberculosis was reported in 2 patients in the CT-P13 arm and in 1 patient in the infliximab arm.  As a result, Celltrion’s CT-P13 and the reference product, infliximab are found to be equivalent in terms of AUCT and Cmax,ss in patients with AS. In addition, CT-P13 was well tolerated, with an efficacy and safety profile comparable to that of infliximab up to week 30.  Celltrion also carried out a Phase III clinical trial with CT-P13 for the treatment of rheumatoid arthritis (RA). 606 patients with active RA despite previous treatment with DMARDs including methotrexate were randomized 1:1 to receive either CT-P13 or infliximab (3 mg/kg, 2-hour IV infusion per dose) plus methotrexate and folic acid. The treatment period consisted of a dose-loading phase (weeks 0, 2, and 6) and a maintenance phase (weeks 14, 22, and 30).  The primary endpoint was the proportion of patients achieving 20% improvement in ACR20 at week 30. The exact binomial test with 95% confidence intervals (CIs) for ACR20 within a margin of ±15 % was used to define equivalence between the 2 treatments. Secondary efficacy and safety endpoints (including ACR50/70; frequency of adverse events) were also evaluated.  At week 30, ACR20 response rates were 60.9% for CT-P13 vs 58.6% for infliximab (2% difference; 95% CI) in the intent-to-treat population, and 73.4% vs 69.7% (4% difference; 95% CI) in the per-protocol population. Outcomes for the secondary efficacy and safety endpoints were also comparable as follows:  ACR50 rates in the per-protocol population were 42.3% vs 40.6% (2% difference; 95% CI), and ACR70 rates were 20.2% vs 17.9% (2% difference; 95% CI) in the CT-P13 and infliximab arms, respectively, all indicating equivalence in clinical efficacy at week 30.  AEs considered by the investigators to be related to study treatment were reported for 106 (35.2%) patients and 108 (35.9%) patients in the CT-P13 and infliximab arms, respectively. Related AEs due to infection were reported in 46 (15.3%) patients and 51 (16.9%) patients in the CT-P13 and infliximab arms, respectively. 15 (5%) CT-P13-treated and 17 (6%) infliximab-treated patients experienced at least 1 infusion reaction. Tuberculosis was reported in 3 patients in the CT-P13 arm and in 1 patient in the infliximab arm.  These successful results will most probably help Celltrion to be the company which developed world’s first biosimilar antibody that will be launched in regulated markets. As well-known Dr.Reddy’s Labs’ Reditux which was registered in India, was world’s first biosimilar antibody but could not gain any approvals in regulated markets yet.  Abstracts of both clinical trials are not be subject to embargo and can be accessed from EULAR 2012 abstract searches.  The regulatory application of CT-P13 to European Medicines Agency was submitted on March 2. Meanwhile, Celltrion also made the application in its homeland, Korea in February this year.  Celltrion has several monoclonal antibody biosimilar candidates in its portfolio and the upcoming target will be Roche/Genentech’s Herceptin. 

Source: Celltrion, Woori I&S Research Center