Article

Comparative Pharmacokinetics of HD203, a Biosimilar of Etanercept, with Marketed Etanercept (Enbrel®)

Department of Pharmacology and Clinical Pharmacology, Seoul National University College of Medicine and Hospital, Seoul, South Korea.
BioDrugs (Impact Factor: 2.99). 04/2012; 26(3):177-84. DOI: 10.2165/11631860-000000000-00000
Source: PubMed

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®.

3 Followers
 · 
64 Reads
  • [Show abstract] [Hide abstract]
    ABSTRACT: Biological drugs or biopharmaceutical products, manufactured with or from living organisms using biotechnology, have represented a therapeutic revolution for the control of inflammatory bowel disease (IBD). At present, in this indication and in our country, only two biologicals are approved, infliximab (IFX) and adalimumab (ADA), both of them monoclonal antibodies against tumor necrosis factor alpha. Effectiveness data are strong for both therapies, with maximum levels of scientific evidence. The upcoming expiry date for these biologicals' patents has allowed the potential marketing of so-called biosimilar agents for the IBD indication. While biosimilars are conceptually for biologicals what generics are for chemical drugs, the structural complexity of biosimilars and their biological and manufacturing variability lead to consider validation processes for these two types in humans as highly differential. Thus, in our setting, under the coverage of "Agencia Española del Medicamento y Productos Sanitarios (AEMPS)" (Spanish Agency of MedicinesandMedicalDevices), guidelines issued by the European Medicines Agency (EMA) are to be applied, which states that a number of stages or steps must be overcome in order to obtain approval for a biosimilar agent. However, despite the presence of these recommendations by EMA, which must be met by a biosimilar in order to be licensed in our marketplace, relevant uncertainties persist that only future decisions by EMA and AEMPS may clarify. The present stance by our task force is that biosimilar development should be undertaken according to established regulations, thus certifying their efficacy and safety. Similarly, this task force considers that results obtained from studies in rheumatoid arthritis (RA) should not be extrapolated to IBD since the biological variability of these complex structures will not ensure a lack of noticeable changes in efficacy and safety.
    No preview · Article · Jan 2013 · Revista espanola de enfermedades digestivas: organo oficial de la Sociedad Espanola de Patologia Digestiva
  • [Show abstract] [Hide abstract]
    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.
    No preview · Article · Mar 2013 · Autoimmunity reviews
  • Source
    [Show abstract] [Hide abstract]
    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.
    Full-text · Article · Sep 2013 · Alimentary Pharmacology & Therapeutics
Show more