Drug Shown to be Effective and Safe in Patients with Immune Thrombocytopenic Purpura (ITP), an Autoimmune Condition Resulting in Decreased Blood Platelets
Alternative Bleeding Assessment Methodology May be Useful in Patients with ITP
Dec 12, 2005
Data from a Phase II study of eltrombopag, an oral investigational drug that increases the production of platelets, demonstrate that the compound was effective in increasing platelet counts in patients with chronic Immune Thrombocytopenic Purpura (ITP), a disorder characterized by episodes of frequent spontaneous bruising, mucosal bleeding, and in severe cases intracranial hemorrhage, and acute episodes of severe bleeding. The data were presented by James B. Bussel, M.D. director of the Platelet Disorders Center, Children's Blood Foundation Division at NewYork-Presbyterian Hospital/Weill Cornell Medical Center at the "Seventh Review of Immune Thrombocytopenic Purpura: Current Issues in Pathogenesis, Diagnosis and Management." The annual symposium is held in connection with the 47th Annual Meeting of the American Society of Hematology (ASH).
In the current double-blind randomized study, 104 adult ITP patients who had failed one prior therapy and had a platelet count 30,000/µL, were randomly assigned to take oral eltrombopag 30 mg, 50 mg, 75 mg, or placebo once daily for six weeks. The study found that eltrombopag at doses of 50 mg and 75 mg was significantly better than placebo (P 0.001) at increasing and maintaining platelet counts to a level that would reduce the risk of bleeding and bruising. The drug increased platelet levels quickly, with up to 87 percent of responders raising their counts by day 15. Response was defined as a platelet count of 50,000/µL. At the end of six weeks of dosing, there were no safety and tolerability events that would preclude the advancement to future studies.
"The results of this trial are very encouraging, given that there are currently no oral treatment options available for ITP that increase the platelet count in such a high percentage of often difficult patients with apparently so little toxicity," said Dr. Bussel, who is the principal investigator of the study and professor of pediatrics at Weill Medical College of Cornell University. "Eltrombopag may offer physicians an effective and convenient treatment alternative because current therapies, such as steroids and platelet transfusions, can have unwanted side effects, must be given IV, or are not sustainable over the long-term."
Eltrombopag is an investigational small-molecule thrombopoietin receptor agonist that is thought to stimulate the proliferation and differentiation of megakaryocytes, the bone marrow cells that give rise to blood platelets, and thus is considered a platelet growth factor. Because it is a small molecule, the drug has less potential than large protein molecules for causing an immune system reaction. Eltrombopag is being developed by GlaxoSmithKline.
A reduction in platelet count is the defining characteristic of any type of thrombocytopenia. Immune thrombocytopenic purpura the condition for which eltrombopag was tested in this study is an autoimmune disorder that is marked by platelet destruction or inadequate platelet production. Sometimes the onset of symptoms is unpredictable; patients may be asymptomatic and diagnosed following a routine blood test. Thrombocytopenia also can occur as a consequence of chemotherapy treatment, interferon treatment, or chronic liver disease.
"ITP can take a significant emotional toll on patients and their families the risk of bleeding is common and patients often feel vulnerable and fatigued," added Dr. Bussel. "New approaches are needed that will help patients to manage this chronic disease and enable them to partake in normal everyday activities without worrying about their health."
New Bleeding Assessment Methodology
Results of a study of ITP patients using a new bleeding assessment methodology developed by Dr. Bussel were also shown in a poster presentation at the ASH meeting. Dr. Bussel developed a scoring method for assessing bleeding in ITP to test the relationship among site-specific bleeding severity (BLS), platelet count, and platelet size.
In the study, patients received a bleeding score based on evaluation of eleven sites. Patients received a BLS grade for each site on a defined scale from no bleeding to "major bleeding." In addition, platelet counts and large platelets were measured. The bleeding score was validated by the relationship of site specific bleeding severity compared to platelet count and the high degree of independent observer reliability. The significance of large platelets remains unclear. The assessment tool takes about three to five minutes to complete.
An internationally recognized leader in clinical trials for ITP, Dr. Bussel is director of the Platelet Disorders Center at NewYork-Presbyterian Hospital/Weill Cornell Medical Center. He is also the principal investigator for the Phase II study of eltrombopag in ITP. The Center's goal is to improve treatments and understanding of the pathophysiology of thrombocytopenia, especially immune thrombocytopenic purpura, or ITP. He has published more than 100 articles on ITP including in the New England Journal of Medicine.
NewYork-Presbyterian Hospital/Weill Cornell Medical Center
The NewYork-Presbyterian Hospital/Weill Cornell Medical Center, located in New York City, is one of the leading academic medical centers in the world, comprising the teaching hospital NewYork-Presbyterian Hospital and its academic partner Weill Medical College of Cornell University. NewYork-Presbyterian/Weill Cornell provides state-of-the-art in-patient, ambulatory, and preventive care in all areas of medicine, and is committed to excellence in patient care, research, education, and community service.