Managed Care - January 2009 - (Page 47)

TOMORROW’S MEDICINE Orphan Disease Gains Second Treatment Option Advances in biologic and small molecule medicine result in two different types of treatments that target the same cell receptor Thomas Morrow, MD T here are dramatic differences between biologic drugs and small molecules. Biologically-derived drugs require manipulation of an organism’s genetic code. The organism, a bacterium, yeast cell, or mammalian cell, then creates the protein. A manufacturer seeks to isolate the protein, purify it, and eventually turn it into a viable treatment. In the case of mammalian cells, the protein is secreted into the surrounding environment. In smaller organisms, the protein must be obtained by destroying the cell walls of the organism, but this makes isolating the desired protein from the slop that is left over quite difficult. Small molecules, on the other hand, are synthesized by using complex chemical reactions from a variety of substrates that may have an organic or inorganic origin. They are much simpler molecules in general. Given these differences, it is rare to find a biologic and a small molecule that target the same receptor, and accomplish the same goal. But this is exactly what occurred recently when the FDA approved eltrombopag, released under the brand name Promacta. It is a thrombopoietin receptor agonist indicated for the treatment of thrombocytopenia in patients with chronic immune (idiopathic) thrombocytopenic purpura (ITP) who have not responded to corticosteroids, immunoglobulins, or splenectomy. manufactured by Amgen and marketed under the brand name Nplate. Nplate is also approved to treat patients with ITP. However, romiplostim is an Fc-peptide fusion protein produced by recombinant DNA technology using E. coli. The treatment activates the intracellular transcriptional pathway leading to increased platelet production by way of the thrombopoietin (TPO) receptor. As is the case with most biologic drugs, romiplostim is given by injection. Eltrombopag, on the other hand, is an orally bioavailable small molecule TPO–receptor agonist. It interacts with the transmembrane domain of the human TPO-receptor and initiates signaling cascades that induce proliferation and differentiation of megakaryocytes from the bone marrow progenitor cells. Chronic and acute ITP is an autoimmune disease affecting approximately 200,000 people in the United States. It is characterized by low platelet counts because of an increase in destruction and reduction of platelet production. The cause is unknown. There are two basic types of ITP, acute and chronic. The chronic form has posed the largest challenge to treat and is associated with an increased tendency to bleed as the platelet count drops to a critical low level. All traditional therapies have focused on the destruction component of the disease and include immune modulation with corticosteroids, intravenous immunoglobulin (IVIG), splenectomy, cyclosporine, and in some cases targeted B cell destruction. Eltrombopag was studied in two (A and B) separate multicenter, randomized, doubleblind, placebo-controlled clinical trials involv- Oral or injected Those of you who consistently read this column may recall an article published in October 2008 that highlighted the drug romiplostim, Thomas Morrow, MD, is the immediate past president of the National Association of Managed Care Physicians. He has 24 years of managed care experience at the payer or health plan level. JANUARY 2009 / MANAGED CARE 47

Table of Contents Feed for the Digital Edition of Managed Care - January 2009

Managed Care - January 2009 Editor's Memo Contents Legislation & Regulation News and Commentary Medication Management Compensation Monitor Health Care's Disruptive Innovations Q&A With Clayton Christensen 'Disruption' May Be Plans' Best Bet Avoid the PBM Rebate Trap HealthPartners Puts Diabetes on Notice Formulary Files Plan Watch Tomorrow's Medicine Ad Index Outlook Unmet Needs in the Management of Plaque Psoriasis Impact of RSV: Implications for Managed Care

Managed Care - January 2009

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