Etanercept

Etanercept is a recombinant human soluble Wyeth under the trade name Enbrel in two separate formulations, one in powder form, the other as a pre-mixed liquid.

Development

Etanercept was developed by researchers at biotechnology company monoclonal antibody against TNFα to be marketed for clinical use. Etanercept is a dimeric molecule, and this dimeric structure is necessary for its proper therapeutic activity. During its development at Immunex Corporation an earlier monomeric version did not have sufficient biologic activity.

Mode of action

Tumor necrosis factor-alpha (TNFα) is a cytokine produced by monocytes and macrophages, two types of white blood cells. It mediates the immune response by increasing the transport of white blood cells to sites of inflammation, and through additional molecular mechanisms which initiate and amplify inflammation. Inhibition of its action by etanercept reduces the inflammatory response which is especially useful for treating autoimmune diseases.

There are two types of TNF receptors: those found embedded in white blood cells that respond to TNF by releasing other cytokines, and soluble TNF receptors which are used to deactivate TNF and blunt the immune response. In addition, TNF receptors are found on the surface of virtually all nucleated cells (red blood cells, which are not nucleated, do not contain TNF receptors on their surface). Etanercept mimics the inhibitory effects of naturally occurring soluble TNF receptors, the difference being that etanercept, because it is a fusion protein rather than a simple TNF receptor, has a greatly extended half-life in the bloodstream, and therefore a more profound and long-lasting biologic effect than a naturally occurring soluble TNF receptor.

Structure

Etanercept is made from the combination of two naturally occurring soluble human 75-kilodalton TNF receptors linked to an Fc portion of an IgG1. The effect is an artificially engineered dimeric fusion protein.

Administration

Enbrel is marketed as a orally, because the digestive system would destroy the drug. FDA approved dose is 25 mg BIW (twice weekly) or 50 mg QW (once weekly).

Safety

According to the product labeling of infliximab, etanercept, and adalimumab, these drugs are in the class of immunosuppressants. After a number of studies and reports of adverse reactions in patients receiving anti-TNF alpha therapy (including serious and sometimes fatal blood disorders, infections, rare reports of lymphoma and solid tissue cancers, rare reports of serious liver injury, and rare reports of demyelinating central nervous system disorders), rare reports of congestive heart failure, the U.S. FDA-approved), these mABs also carry black-box warnings which are not shared by etanercept. In addition infliximab has a higher propensity for the development of anaphylaxis, perhaps as a result both of its chimeric structure and its intravenous route of administration.

Sales

Enbrel is the most widely used anti-TNF biologic drug in the field of rheumatology with more patients taking this drug for that indication than either Remicade (Certolizumab pegol is a fourth biologic anti-TNF therapeutic which is currently awaiting FDA-approval in the U.S., for an initial indication of Crohn's Disease.

Similar agents

• Infliximab
• Adalimumab
• Certolizumab pegol

See also

• Albert Lasker Award for Clinical Medical Research
• Amgen
• Biotechnology
• Cytokine
• Cytokine storm
• Edward Tobinick
• Interleukins
• Interferon
• Ravinder N. Maini
• Tumor necrosis factors