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"Prediction is very difficult, especially if it's about the future." Nils Bohr Leading pharmaceutical companies invest billions of dollars each year in research and development with little or no guarantee of a return on their investment. With the average cost of developing a new drug... More
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  • GSK: Promacta – Immune Thrombocytopenia Medication

    GlaxoSmithKline's (NYSE:GSK) Promacta (eltrombopag) is an orally delivered small molecule agonist of the c-mpl (TpoR) receptor, which is the physiological target of the hormone thrombopoietin.

    Eltrombopag is used to treat low blood platelet counts in adults with chronic immune (idiopathic) thrombocytopenia (ITP), when either corticosteroids, immunoglobulins or surgery to remove the spleen have not worked well enough.

    The Eltrombopag molecule was discovered as a result of research collaboration between GlaxoSmithKline and Ligand Pharmaceuticals (NASDAQ:LGND). It is currently marketed by GSK under the brand names Promacta in the US and Revolade in Europe.

    Designated an orphan drug in the USA and European Union, since the chronic ITP population is under 200,000 in both the US and Europe. Promacta was approved by the FDA in November 2008.

    Treatment Regimen

    Promacta is supplied as a tablet designed for oral administration. The recommended initial dose of the drug is 50 mg once daily except in patients who are of East Asian ancestry or who have moderate to severe hepatic impairment. In this population, and for patients with moderate or severe hepatic impairment, the recommended initial dose of Promacta is 25 mg once daily.

    Promacta should be adjusted to achieve and maintain a platelet count >50 x 109/L as necessary to reduce the risk for bleeding. The dosing of Promacta should not exceed 75 mg daily.

    Clinical Efficacy

    In preclinical studies, Eltrombopag was shown to interact selectively with the thrombopoeitin receptor, leading to activation of the JAK-STAT signaling pathway and increased proliferation and differentiation of megakaryocytes. Animal studies confirmed that administration could increase platelet counts.

    In Phase 1 clinical studies, in 73 healthy volunteers, higher doses of eltrombopag caused larger increases in the number of circulating platelets without tolerability problems.

    Eltrombopag has been studied, and shown to be effective, in two major clinical syndromes: idiopathic thrombocytopenic purpura and cirrhosis due to hepatitis C (in which low platelet counts may be a contraindication for interferon treatment).

    After 6 weeks of therapy in a phase 3 trial, eltrombopag 50mg/day was associated with a significantly higher response rate than placebo in adult patients with chronic ITP.

    Side Effects

    Eltrombopag side effects may include, but are not limited to, hemorrhage, nausea, vomiting, menorrhagia, myalgia, paresthesia and cataract.

    Systematic (IUPAC) Name

    3'-{(2Z)-2-[1-(3,4-dimethylphenyl)-3-methyl-5-oxo-1,5-dihydro-4H-pyrazol-4-ylidene]hydrazino}-2'-hydroxy-3-biphenylcarboxylic acid

    Oct 11 7:14 AM | Link | Comment!
  • Amgen: Nplate – Immune Thrombocytopenia Medication

    Amgen's (NASDAQ:AMGN) Nplate (Romiplostim) is a man-made (recombinant) protein medicine used to treat low blood platelet counts in adults with chronic immune thrombocytopenia (ITP), when certain other medicines, or surgery to remove your spleen, have not worked well enough.

    The Romiplostim molecule was developed by Amgen and is marketed under the trade name Nplate through a restricted usage program called NEXUS. During development and clinical trials the drug was called AMG531.

    (click to enlarge)

    Romiplostim was designated an orphan drug status by the FDA in 2003, since the chronic ITP population in the USA is under 200,000.

    In August, 2008, the FDA approved romiplostim as a long-term treatment for chronic ITP in adults who have not responded to other treatments, such as corticosteroids, intravenous immunoglobulin, Rho(NYSE:D) immune globulin or splenectomy.

    Treatment Regimen

    Romiplostim treatment is generally administered at weekly intervals via subcutaneous injection. Prior to injection, a complete blood count (CBC) is obtained, as the dosage is dependent on the individual's body weight and platelet count at the time of treatment.

    The goal of treatment is to maintain the count above 50,000 per cubic millimeter (mm3) of blood, not to achieve a normal count-defined as 150,000-450,000 per mm3 in most healthy individuals.

    If a count of 200,000 or higher is achieved for two consecutive weeks a reduced dose is administered or treatment is suspended until the count decreases below 200,000.

    Clinical Efficacy

    In well designed, 24-week, Phase III trials, romiplostim was significantly more effective than placebo in achieving the primary endpoint of a protocol-defined durable platelet response in nonsplenectomized or splenectomized adults with chronic immune thrombocytopenic purpura.[6]

    Side Effects

    Romiplostim's effect is to stimulate the patient's megakaryocytes to produce platelets at a more rapid than normal rate, thus overwhelming the immune system's ability to destroy them.

    Since doing so involves changes to the bone marrow chemistry, a number of potentially serious side-effects may develop, including myalgia, joint and extremity discomfort, insomnia, thrombocytosis, which may lead to potentially fatal clots, and bone marrow fibrosis.

    Systematic (IUPAC) name

    L-methionyl[human immunogloblin heavy constant gamma 1-(227 C-terminal residues)-peptide (Fc fragment)] fusion protein with 41 amino acids peptide, (7-7′:10,10′)-bisdisulfide dimer.

    Oct 11 5:15 AM | Link | Comment!
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