Purpose: 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. Experimental Design: 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 109/L throughout the studys 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.

This study will provide chronic hepatitis C patients with low platelets (less than 75x10\^9/L) the opportunity to undergo treatment and possible cure of their virus. The main hepatitis C drugs will be administered as standard of care, with the addition of the study drug eltrombopag.

The investigators hypothesize that providing eltrombopag to chronic hepatitis C patients with low platelets (less than 75x10\^9/L) will permit the initiation and completion of antiviral triple therapy with boceprevir, ribavirin, and pegylated-interferon.

Eltrombopag has been used in the treatment of immune thrombocytopenia (ITP), and significantly increased platelet count and decreased fatal hemorrage. As it's known that all patients with acute leukemia will experience bone marrow suppression and thrombocytopenia after chemotherapy. Some patients even died of fatal bleeding during this period for lacking of platelet transfusion or platelet transfusion refractoriness. So a lot needs to be done to shortern thrombocytopenia time or reduce fatal hemorrage incidence after chemotherapy in acute leukemia patients. In this prospective randomized controlled study, the effect and safety of eltrombopag in the treatment of thrombocytopenia after consolidation therapy in acute myeloid leukemia (AML) is evaluated.

The purpose of this study is to determine the response rate and response duration with the combination of eltrombopag and high-dose dexamethasone

A clinical study to evaluate the efficacy of a drug called eltrombopag in adult patients affected of primary immune thrombocytopenia as first treatment to address the disease.

The goal of this clinical research study is to learn if eltrombopag can help to increase the number of platelets in patients with CLL. The safety of this drug will also be studied.

Bioequivalence Study

Immune thrombocytopenia is an immune condition where antibodies are produced against platelets. Eltrombopag is a thrombopoietin receptor agonist that stimulates and promotes platelet production approved for treating thrombocytopenia in patients with chronic immune thrombocytopenia, where other treatments as corticosteroids, splenectomy or immunoglobulins are inadequate. The aim of this meta-analysis was to evaluate the efficacy and safety of the eltrombopag in adults and children with immune thrombocytopenia. We included 7 studies with a total of 765 patients (606 adults and 159 children). We evaluated the number of patients that achieved a post treatment platelet count equal or above 50x109 /L (primary result-target) without the need of rescue treatment for at least 4 weeks. Our data showed that patients who received eltrombopag were almost 4 times more probable in achieving the primary target when compared to patients that received placebo (RR 3.84, 95% CI 2.39 to 6.14; I2 = 46%). The number of patients that needed rescue treatment and the number of bleeding incidents were reduced in the group that received eltrombopag when compared to those who received placebo (RR 0.40, 95% CI 0.25 to 0.62; I2 = 40%) (RR 0.74, 95% CI 0.62 to 0.89; I2 = 68%). The total number of side effects did not statistically differ between the two groups (RR 0.99, 95% CI 0.90 to 1.08; I2 = 14%). Our findings were similar to previously published studies and confirm that eltrombopag is safe and efficient in immune thrombocytopenia. However more clinical trials are needed in order to enhance our findings.

Eltrombopag, an oral thrombopoietin receptor agonist, can increase platelets in patients with chronic immune thrombocytopenic purpura and produces trilineage responses in patients with refractory aplastic anemia. Because management of persistent cytopenias in MDS patients remains unsatisfactory, we initiated a pilot, phase II study of eltrombopag in low to Int-2 risk MDS subjects, following failure of standard therapies, or as an initial therapy (NCT00961064). Eltrombopag was initiated at 50 mg/day, increasing every two weeks to 150mg/day. The primary endpoint assessed at 16 weeks was defined as: (a) platelets ≥ 20,000/μL above baseline or stable platelet counts with transfusion independence for a minimum of 8 weeks in transfusion dependent subjects; or (b) in anemic subjects (Hb < 9 g/dL pretreatment) ≥ 1.5g/dL increase in Hb without transfusion support, or a reduction in the units of PRBC transfusions by at least 50%; or (c) in neutropenic subjects (ANC <0.5 x 109/L pretreatment) ≥ 0.5 x 109/L increase in ANC, or ≥ 100% increase. Responding subjects could continue to receive eltrombopag on an extension arm. Eighteen subjects are evaluable to date, with a median age 65 years (range 35 - 85), a male predominance (11/18), and refractory cytopenia with unilineage dysplasia (RCUD) as the most common subtype (8/18). At baseline, 9 subjects had normal cytogenetics, and 7 had abnormalities including deletion 13q, trisomy 6, deletion 20q, and trisomy 15. Bone marrow blasts were <5% in all subjects pre-treatment. Severe thrombocytopenia was the qualifying cytopenia in 9 subjects, severe anemia in 3, and 6 were bicytopenic. Eltrombopag was well tolerated by all subjects, with only one grade 3 adverse event (hepatotoxicity) that resolved without dose-reduction. All but one subject reached the full dose of 150mg/day. 56% (10/18) of patients achieved a response at 16 weeks, and most were eventually bi- or tri-lineage, with continued improvement in counts with longer duration of treatment beyond the 16 week endpoint. Eltrombopag was discontinued in 3 subjects who essentially normalized counts (Hb >10 g/dL and platelets >50,000/μL and ANC>1000/μL) during the extension arm, with maintenance of improved blood counts off drug for a median of 4 months (range 3 - 24). Only one subject (a responder) had progression of MDS on eltrombopag, with marrow blasts of 8% noted at 9 months. Accrual to the study is continuing, and preliminary results indicate eltrombopag is a promising, welltolerated and effective drug to improve cytopenias of all lineages in MDS patients.

Background: Eltrombopag, a thrombopoietin receptor agonist, was approved in 2008 for the treatment of immune thrombocytopenic purpura. More recently, benefits demonstrated in the proliferation and maintenance of hematopoietic stem and progenitor cells (HSTC) led to its use and approval in the treatment of severe aplastic anemia (AA) refractory to immunossupressive therapy. Aims: In this report, we evaluated response to eltrombopag in patients with refractory AA and associated side effects. Methods: Retrospective analysis of six patients with a diagnosis of aplastic anemia and thrombocytopenia (platelet count ≤30.000/uL), refractory to imunossupressive therapy and ineligible for allotransplant, treated with eltrombopag. Patients characteristics, response, clinical evolution and adverse effects were evaluated. Results: Four patients were female and median age at diagnosis was 66 years (36-76). Previous treatments included horse antithymocyte globulin (1), cyclosporine (4), intravenous immunoglobulin (1), corticosteroids (4) and danazol (1). Treatment with eltrombopag was associated to cyclosporine in four patients; two cases had chronic renal failure and consequent contraindication to cyclosporine. The median duration of treatment with eltrombopag at the time of this analysis was 7 months (3-12). At 3 months, all patients had platelet counts >30.000/uL (median increase, 16.500/uL). Five patients improved hemoglobin levels (median increase, 2.2g/dL); 3 of them were previously dependent on red cell transfusions, and no longer needed transfusions. Four patients increased neutrophil counts (median increase, 1110/uL). All but one patient received a maximum dose of 150mg per day. Only one patient needed temporary discontinuation due to hepatic abnormalities, that were rapidly resolved. One other patient had mild elevation of liver enzyme levels. No other relevant side effects occurred. Summary/Conclusions: Treatment with eltrombopag was associated with hematologic response of one or more hematopoietic lineage, independence of blood transfusions and improved quality of life of patients with refractory severe AA. Except for infrequent and reversible hepatic abnormalities, tolerability was excellent. Thus, eltrombopag might be used in situations where other measures have failed in patients who have no indication for allogeneic stem cell transplant. A caution, however, should be taken on the risk for clonal evolution that should be carefully screened and surveilled.