GlaxoSmithKline initiates study of PROMACTA in chronic idiopathic thrombocytopenic purpura

GlaxoSmithKline has announced the initiation of a global, open-label, single group trial that will assess the efficacy, safety and tolerability of PROMACTA (eltrombopag olamine) in patients previously treated for chronic idiopathic thrombocytopenic purpura (ITP).

The trial, called REPEAT (Repeat ExPosure to Eltrombopag in Adults with Idiopathic Thrombocytopenic Purpura), will evaluate a repeated dosing schedule of three six week cycles of PROMACTA treatment in 50 patients with chronic ITP who will be enrolled at multiple centers.

"The current treatment approaches to acutely increase the platelet count typically include treatment with steroids or IV gammaglobulin, both of which may have issues with tolerability or safety," says James B. Bussel, MD, Director of the Platelet Disorders Center, Children's Blood Foundation Division at the New York-Presbyterian Hospital/Weill Cornell Medical Center and investigator for this trial. "Due to patients' varying clinical circumstances, it is important to validate the safety and effectiveness of repeated short-term treatment with eltrombopag in patients with chronic ITP."

ITP is estimated to affect 50 to 100 new persons per million per year in the United States and Europe. People with ITP often bleed from small blood vessels underneath the skin causing bruises, nosebleeds, bleeding from the gums during dental work, or other bleeding that is difficult to stop. Bleeding in the brain or gastrointestinal (GI) tract is rare but can be life threatening if it occurs. Although this condition can be managed chronically, it is associated with significant mortality and morbidity -- 5% of patients will die within ten years of diagnosis, primarily from intracranial hemorrhage.

Initiation of the REPEAT trial follows completion of a Phase II study that evaluated 117 patients with chronic ITP and low platelet levels (<30,000/microliter). The Phase II results showed a statistically significant increase (p=0.001) in the number of patients achieving a platelet count greater than or equal to 50,000/microliter and decreased bleeding following PROMACTA doses of >50mg over six weeks. In Phase II, PROMACTA was not associated with an increased incidence of adverse events (AEs) compared to placebo across the 30mg, 50mg and 75mg eltrombopag treatment arms. Bleeding adverse events included the following: hemorrhoids, hemorrhagic diarrhea and conjunctival hemorrhage in 3 patients receiving placebo; epistaxis, gingival bleeding and contusions in 5 patients receiving 30mg of PROMACTA; menorrhagia in 1 patient receiving 50mg of PROMACTA; and contusion in 1 patient receiving 75mg of PROMACTA. All 7 patients who received PROMACTA and bled were non-responders. The most common AE observed in this study was mild to moderate headache, reported in 21% of subjects on placebo, and 13%, 10% and 21% of subjects in the 30mg, 50mg and 75mg PROMACTA arms, respectively.

"We are extremely encouraged by the continued progress in our PROMACTA clinical development program", said Paolo Paoletti, MD, Senior Vice President, Oncology Medicine Development Center, GSK. "We continue to be very optimistic about PROMACTA and we expect results from this trial will represent another step towards providing patients with a safer, more effective ITP treatment."

In December 2006, GlaxoSmithKline announced the initiation of a Phase III trial assessing the safety, efficacy and tolerability of PROMACTA in a long- term setting (up to six months) in previously treated patients with chronic ITP. Long-term ITP treatment may be necessary in patients with consistently low platelet levels and current treatment options such as steroids have draw- backs if used on a long-term basis. Therefore, it is important to evaluate PROMACTA in this setting.

Results from other studies involving PROMACTA will be presented at international medical congresses in the near future and additional studies are ongoing and planned in ITP and other conditions where thrombocytopenia is an issue. PROMACTA is an investigational agent that is not approved for use in any market for any indication at this time.

The REPEAT trial will assess the efficacy, safety, and tolerability of three repeated dosing cycles of PROMACTA in patients previously treated for chronic ITP, examples of which include splenectomy, corticosteroids, immunoglobulins, cyclophosphamide or rituximab. The primary objective is to evaluate the effect of PROMACTA on platelet counts during three consecutive treatment cycles. Secondary objectives include evaluating incidence and severity of bleeding, as well as the frequency of adverse events.

PROMACTA is a non-peptide thrombopoietin receptor agonist that has been shown in pre-clinical research and clinical trials to stimulate the proliferation and differentiation of megakaryocytes, the bone marrow cells that give rise to blood platelets, and thus maybe considered a platelet growth factor. PROMACTA is administered orally as a once a day tablet. The safety profile will be further examined in the ongoing clinical trials. PROMACTA was discovered as a result of a research collaboration between GlaxoSmithKline and Ligand Pharmaceuticals. It is being developed by GlaxoSmithKline. PROMACTA is an investigational compound that has not received regulatory approval in any market for any indication at this time.

ITP is characterized by increased autoimmune platelet destruction and/or inadequate platelet production. Its cause is currently unknown. Some patients with ITP are asymptomatic or have mild bruising while others develop mucosal bleeding that can become severe. A normal blood platelet count is greater than or equal to 150,000/microliter and less than or equal to 400,000/microliter. A reduction in platelet count (to a level <150,000/microliter) is the defining characteristic of any type of thrombocytopenia and diagnosis can be confirmed following a routine blood test.

Thrombocytopenia can occur as a consequence of an autoimmune abnormality, a bone marrow disease, chemotherapy treatment, interferon treatment, viral infection or chronic liver disease. Thrombocytopenia can impede a variety of medical treatments. It can prevent cancer patients from receiving their full dose of chemotherapy, preclude patients with hepatitis C infection from receiving interferon therapy or lead to dose reductions or discontinuation, and complicate surgical or dental procedures.