Comparative pharmacokinetics of HD203, a biosimilar of etanercept, with marketed etanercept (Enbrel®): a double-blind, single-dose, crossover study in healthy volunteers.
ABSTRACT HD203 is a biosimilar of etanercept, a fusion protein of the ligand-binding portion of the human tumor necrosis factor receptor II linked to the Fc portion of human immunoglobulin G1. Since HD203 is under clinical development, this study was conducted to compare the pharmacokinetics of HD203 with Enbrel®, the first marketed etanercept.
A double-blind, randomized, single-dose, two-period, two-sequence, crossover study was conducted in 37 healthy volunteers. In each period, 25 mg/mL of reconstituted lyophilized reference (Enbrel®) or test product (HD203) was administered subcutaneously, either the reference product followed by the test product, or vice versa. Serial blood samples for pharmacokinetic analysis were taken for 480 hours after dosing, and serum concentrations of the products were determined using a commercial enzyme-linked immunosorbent assay. The geometric mean ratios with 90% confidence intervals for the maximum concentration (C(max)) and the area under the concentration-time curve from time 0 to the last measurable time point (AUC(0-t)) were estimated.
A total of 35 subjects completed the study; serious adverse events were not observed. The mean serum concentration-time profiles of the two products were similar. The C(max) and AUC(0-t) values of the reference product (mean ± standard deviation) were 1.25 ± 0.45 mg/L and 283.15 ± 98.57 mg*h/L, respectively, while those of the test drug were 1.35 ± 0.47 mg/L and 315.78 ± 99.38 mg*h/L, respectively. The geometric mean ratios (90% confidence intervals) of the test to the reference for C(max) and AUC(0-t) were 1.08 (1.00, 1.16) and 1.13 (1.05, 1.21), respectively.
A single subcutaneous injection of HD203 or Enbrel® into healthy volunteers appeared to be safe and well tolerated. Comparative pharmacokinetics demonstrated that reconstituted lyophilized HD203 has bioavailability similar to that of Enbrel®.
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ABSTRACT: The last two decades have witnessed a revolution in the treatment of autoimmune diseases due to the introduction of biological agents which, although now included as standard treatment in patients with autoimmune rheumatological, dermatological and gastrointestinal diseases. The use of biological agents is associated with greater costs compared with the mainly anti-inflammatory and immunosuppressant drugs used in the pre-biological era. Biosimilars are highly similar copies of biological drugs, but not identical to approved 'reference' agents. Biological agents are complex proteins involved in the immune response and their exact replicas are extremely difficult, if not impossible, to obtain. Three scenarios have converged to provide a specific opportunity for biosimilars in autoimmune diseases: growing demand for biologics due to successful clinical use; the nearing of patent expiry for the four top-selling biological brands; and the search to reduce health costs due to the financial crisis. We aimed to review the crucial topics of efficacy, safety and regulatory approach of upcoming biosimilars.Autoimmunity reviews 03/2013; 12(10). DOI:10.1016/j.autrev.2013.02.005 · 7.10 Impact Factor
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ABSTRACT: A biosimilar is a copy version of an approved original biological medicine whose data protection has expired. To provide an overview of the development of biosimilars worldwide. Literature review of manufacturing processes of biosimilars, differences and similarities between biosimilars and the reference product, approval pathways for biosimilars, challenges in clinical trial study design and available data from clinical trials. Biosimilars have the same amino acid sequence and highly similar glycosylation patterns that overlap with the originator product. Both efficacy and toxicity are difficult to predict due to subtle molecular changes that might have profound effects on clinical efficacy, safety and immunogenicity. Their main advantage is related to cost savings. Direct evidence of safety and benefit from clinical trials, post-marketing pharmacoviligance and unequivocal identification of the product as a biosimilar are requirements before approval. Non-inferiority or equivalence trials are required by regulatory agencies. Over the past years, several biosimilars have been approved such as erythropoietin or growth factors. Recently, two monoclonal antibodies, Remsima and Inflectra, have been shown to be equivalent to infliximab (INX) in safety and efficacy in rheumatologic conditions. Interchangeability, automatic substitution and switching are key issues when treating patients with biosimilars in clinical practice. Biosimilars represent a new generation of drugs in liver and gastrointestinal diseases. On June 27, 2013, Hospira's Inflectra (INX) was the first biosimilar monoclonal antibody to receive positive opinion from European Medicines Agency's Committee for Medicinal Products for Human Use for rheumatoid arthritis, inflammatory bowel disease and plaque psoriasis.Alimentary Pharmacology & Therapeutics 09/2013; 38(8). DOI:10.1111/apt.12477 · 4.55 Impact Factor
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ABSTRACT: A biosimilar is a copy of an approved biological medicine whose patent protections have expired. Biosimilars of antibodies to tumour necrosis factor α (TNFα) are becoming important in the treatment of inflammatory bowel diseases (IBD). The first one introduced commercially is an infliximab biosimilar. The aim of this study was to provide an overview of anti-TNFα biosimilars. The literature on biosimilars of monoclonal anti-TNFα antibodies was reviewed, including their manufacture and approval pathways, concerns about efficacy, safety, immunogenicity, extrapolation, switching and labelling. Previous experience with biosimilars of epoetin and other growth factors was also reviewed. The infliximab biosimilar CT-P13 was the first biosimilar monoclonal antibody registered for the treatment of IBD. The major advantage of biosimilars is the reduced cost of therapy. Concerns have arisen, however, about the efficacy and safety of CT-P13 in IBD, the extrapolation of results from rheumatologic trials to IBD and the free interchangeability of CT-P13 with infliximab. Experience with simple peptide biosimilars, such as epoetins and growth factors, has generally been positive, with these biosimilars having similar efficacy and safety as the original products, although immunogenicity remains a major concern. Upcoming postregistration studies will address concerns on biosimilars in IBD, including their efficacy, safety, immunogenicity, switching and interchangeability. Biosimilars active against the same epitopes, but with improved pharmacokinetic properties that enhance their efficacy and/or safety, may be the next stage in the development of biosimilars. Anti-TNFα biosimilars represent promising new treatment options for patients with IBD. However, data on their efficacy and safety in IBD are needed.European journal of gastroenterology & hepatology 04/2014; 26(6). DOI:10.1097/MEG.0000000000000098 · 2.15 Impact Factor