A study comparing pharmacokinetics and tolerability of branded etanercept (25 mg) and its biosimilar (25 mg) in Korea reported by Gu et al has shown that the reference drug and the test biosimilar met the standard criteria for assuming bioequivalence as defined by Korean regulatory authorities.
Etanercept is a drug that treats autoimmune diseases by inhibiting tumour necrosis factor (TNF), thereby preventing inflammation caused by TNF. The originator drug Enbrel (Pfizer) is used for the treatment of rheumatoid, juvenile rheumatoid and psoriatic arthritis, plaque psoriasis and ankylosing spondylitis.
In this randomised, open-label, single-dose, active-controlled, two-sequence, crossover study 25 healthy Korean male volunteers aged 20 to 55 years were recruited between November 2008 to February 2009 at the Seoul National University Hospital, South Korea. Subjects were randomised to one of two study groups and received either the biosimilar or the originator drug subcutaneously in their periumbilical area according to their sequence group during the first treatment period. After a wash-out period of one week all subjects then switched to receive the other treatment.
Twenty-three subjects completed at least one treatment period during the study and 21 subjects completed the drug administration and treatment period for each study drug.
Blood samples were collected via cannula inserted into a forearm vein, before dosing at 3, 6, 12, 24, 36, 48, 60, and 72 hours, and from direct injection to a forearm vein at 96, 144, 216, 312, and 480 hours after dosing to evaluate the pharmacokinetics of etanercept.
Eleven of the 21 subjects (52.4%) who received the biosimilar drug and 8 of the 21 subjects (38.1%) who received the originator drug reported 39 adverse events for each. The most frequently reported adverse events were headache (6 cases; 14.3%), throat irritation (4 cases; 9.5%) and epistaxis (4 cases; 9.5%). The moderate drug-related adverse events were cough (2 cases; 4.8%), myalgia (1 case; 2.4%), and skin exfoliation (1 case; 2.4%).
There were four drop-outs during the study, which were not related to study medication. There were no serious adverse events considered as related to study medication. No clinically significant findings were reported in terms of vital signs, laboratory tests, ECGs or physical examinations.
Pharmacokinetic analysis of the drugs showed that both the biosimilar and originator drugs were absorbed with a median time to peak concentration (Tmax) of 72 hours (range, 36–144) and eliminated with a mean half life (% coefficient of variation) of 92.7 (20.9%) and 87.4 (16.6%) hours, respectively. The geometric mean ratios (90% confidence intervals) of the biosimilar to originator drug for peak concentration (Cmax), area under curve (AUC)0–t and AUC0–¥ were 0.99 (0.83–1.17), 0.95 (0.79 –1.13) and 0.95 (0.80 –1.13), respectively.
No differences in tolerability were observed between the brand-name and the biosimilar etanercept. Pharmacokinetic parameters were also shown to be similar between the two drugs. In these healthy Korean males the reference drug and the tested biosimilar met the standard criteria for assuming bioequivalence as defined by Korean regulatory authorities.
This study was carried out in healthy Korean males before investigating the biosimilar in the target group. Therefore the clinical efficacy and safety of biosimilar etanercept should be evaluated in further studies in rheumatoid arthritis patients.
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