title: Eltrombopag for the treatment of chronic immune (idiopathic) thrombocytopenic purpura.
abstract: OBJECTIVE
  On November 20, 2008, eltrombopag (Promacta) received approval from the US Food and Drug Administration (FDA) for the treatment of thrombocytopenia in patients with chronic immune thrombocytopenic purpura (ITP) who have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy. This report summarizes the FDA analyses of the clinical data supporting this approval.
  
  
  METHODS
  The FDA reviewed data from two double-blind, placebo-controlled clinical studies, an uncontrolled extension study, and exploratory supportive studies. One study randomized patients among placebo or one of three daily doses of eltrombopag (30, 50, or 75 mg). The other study randomized patients between placebo or eltrombopag, 50 mg daily. Study drugs were administered for 6 weeks. The primary endpoint was response rate. Patients who completed these and other studies were eligible to enroll in the extension study.
  
  
  RESULTS
  Overall, 231 patients were randomized within the two controlled studies (67 to placebo; 164 to eltrombopag). A platelet response was observed among 59% and 70% of the patients receiving eltrombopag, 50 mg daily. Corresponding placebo response rates were 16% and 11%, respectively. Serious hemorrhages occurred among two patients receiving eltrombopag and one patient receiving placebo, and among five patients following discontinuation of eltrombopag. In the extension study, eltrombopag was administered to 109 patients; median platelet counts were > 50 x 10(9)/L throughout the study's quarterly follow-up points. Major safety findings pertained to a risk for hepatotoxicity, worsened thrombocytopenia with hemorrhage following eltrombopag discontinuation, and bone marrow reticulin formation.
  
  
  CONCLUSIONS
  The US FDA approved eltrombopag for use among certain patients with chronic ITP based upon demonstration of a favorable risk-to-benefit profile, where the major benefit pertained to demonstration of a clinically important increase in blood platelets among a population of patients relatively refractory to prior therapies.
authors.affiliation: Office of Oncology Drug Products, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland 20993, USA. andrew.dmytrijuk@fda.hhs.gov
authors.forename: Andrew
authors.initials: A
authors.lastname: Dmytrijuk
authors.forename: Kathy
authors.initials: K
authors.lastname: Robie-Suh
authors.forename: Dwaine
authors.initials: D
authors.lastname: Rieves
authors.forename: Richard
authors.initials: R
authors.lastname: Pazdur
mesh_terms: D001565:Benzoates / Q000009:adverse effects / Q000627:therapeutic use*; D002908:Chronic Disease; D017277:Drug Approval; D006801:Humans; D006834:Hydrazines / Q000009:adverse effects / Q000627:therapeutic use*; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000188:drug therapy*; D011720:Pyrazoles / Q000009:adverse effects / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome
chemical_list: D001565:Benzoates; D006834:Hydrazines; D011720:Pyrazoles; C520809:eltrombopag