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GlaxoSmithKline Halts Study of Eltrombopag (Promacta) in People with Liver Disease Due to Blood Clot Risk

SUMMARY: The U.S. Food and Drug Administration (FDA) and GlaxoSmthKline (GSK) have issued a safety advisory regarding eltrombopag (Promacta), a thrombopoietin receptor agonist used to treat thrombocytopenia, or low platelet count, which can cause excessive bleeding and bruising. After an unexpected number of participants developed blood clots in liver veins, GSK stopped a clinical trial testing eltrombopag in patients with chronic liver disease due to hepatitis B, hepatitis C or other causes.

Below is the text of an alert issued last week by the FDA, followed by a "Dear Health Care Professional" letter from GSK regarding termination of the ELEVATE trial.

Promacta (eltrombopag): Portal Venous System Thromboses in Study of Patients With Chronic Liver Disease

Audience: Hematology healthcare professionals

[Posted 05/12/2010] GlaxoSmithKline and FDA notified healthcare professionals of a new safety finding in patients with thrombocytopenia due to chronic liver disease treated with eltrombopag, a thrombopoietin receptor agonist approved for the treatment of thrombocytopenia in adult patients with chronic immune (idiopathic) thrombocytopenic purpura. The ELEVATE study, a randomized, double-blind, placebo-controlled, multinational study was terminated following the identification of an imbalance of thrombosis of the portal venous system in the patients treated with eltrombopag versus matching placebo. Six patients (4%) in the eltrombopag group and one (1%) in the placebo group experienced a thrombotic event of the portal venous system. Five of the six patients treated with eltrombopag experienced the portal venous thrombosis at platelet counts above 200,000/mcL. GSK has communicated this safety finding to clinical trial investigators and regulatory agencies. GSK is working with regulatory agencies to include this safety information in the label.

Action required by Health Care Professionals:

Health Care Professionals are reminded that Promacta is indicated for the treatment of thrombocytopenia in adult patients with chronic immune (idiopathic) thrombocytopenic purpura (ITP) and is not indicated for the treatment of thrombocytopenia in patients with chronic liver disease.
Treatment with Promacta should be aimed at increasing the platelet count to a level that reduces the risk of bleeding; Promacta should not be used in an attempt to normalize the platelet count.
Use caution when administering Promacta to patients with known risk factors for thromboembolism.
Exercise caution when administering Promacta to patients with hepatic disease. Use a lower starting dose (25mg once daily) of Promacta in patients with moderate to severe hepatic disease and monitor closely.

GLAXOSMITHKLINE SAFETY ADVISORY

Date: May 4, 2010

Dear Health Care Professional,

Promacta (eltrombopag) Notification Of Safety Information: Portal Venous System Thromboses in a Study of Patients With Chronic Liver Disease (ELEVATE)

GlaxoSmithKline (GSK) would like to inform you of a new safety finding concerning eltrombopag in patients with thrombocytopenia due to chronic liver disease.

Promacta is a thrombopoietin receptor agonist approved for the treatment of thrombocytopenia in adult patients with chronic immune (idiopathic) thrombocytopenic purpura (ITP).

Key Messages

In a study of thrombocytopenic patients with chronic liver disease of diverse etiology, patients were treated with eltrombopag 75mg or matching placebo for 14 days prior to undergoing an elective invasive procedure. The study was terminated following the identification of an imbalance of thrombosis of the portal venous system in the patients treated with eltrombopag.

Six patients (4%) in the eltrombopag group and 1 (1%) in the placebo group experienced a thrombotic event of the portal venous system. Five of the six patients treated with eltrombopag experienced the portal venous thrombosis at platelet counts above 200,000/mcL.

The risk for development of thromboembolic events is included in the Warnings and Precautions section of the product information for eltrombopag.

Eltrombopag is indicated for the treatment of chronic immune (idiopathic) thrombocytopenic purpura (ITP) and is not indicated for the treatment of thrombocytopenia in patients with chronic liver disease.

Actions Taken by GlaxoSmithKline

GSK has communicated this safety finding to clinical trial investigators and regulatory agencies. GSK is working with regulatory agencies to include this safety information in the label.

To conduct a comprehensive analysis of the clinical trial data GSK terminated the ELEVATE study. This data has been publicly presented at an international scientific meeting.

GSK's highest priority is patient safety. GSK will continue to review new safety data for eltrombopag, including information arising from clinical trials across all the indications under study and from post-marketing adverse event reports.

Action required by Health Care Professionals

Health Care Professionals are reminded that Promacta is indicated for the treatment of thrombocytopenia in adult patients with chronic immune (idiopathic) thrombocytopenic purpura (ITP) and is not indicated for the treatment of thrombocytopenia in patients with chronic liver disease.

Treatment with Promacta should be aimed at increasing the platelet count to a level that reduces the risk of bleeding; Promacta should not be used in an attempt to normalize the platelet count.

Use caution when administering Promacta to patients with known risk factors for thromboembolism.

Exercise caution when administering Promacta to patients with hepatic disease. Use a lower starting dose (25mg once daily) of Promacta in patients with moderate to severe hepatic disease and monitor closely.

Supporting Information

The ELEVATE study was a randomized, double-blind, placebo-controlled, multinational study conducted to assess the safety and efficacy of eltrombopag to reduce the need for platelet transfusion in thrombocytopenic patients with chronic liver disease undergoing elective invasive procedures.

In this study, thrombocytopenic patients with mild, moderate and severe hepatic impairment of diverse etiology, were treated with eltrombopag 75 mg or matching placebo for 14 days prior to undergoing an elective invasive procedure. Patients with concomitant malignancies were allowed to enroll. An Independent Data Safety Monitoring Committee identified an imbalance of thrombosis of the portal venous system in the patients treated with eltrombopag. GSK terminated the study to conduct a comprehensive analysis of the study data. Six patients (4%) in the eltrombopag group and 1 (1%) in the placebo group experienced a thrombotic event of the portal venous system, and an additional patient in the placebo group was diagnosed with a myocardial infarction. Five of the six patients treated with eltrombopag experienced the portal venous thrombosis at platelet counts above 200,000/µL. This data was presented at an international scientific meeting (European Association for the Study of the Liver, April 2010).

GSK will continue to carefully evaluate all thromboembolic events from clinical trials and post marketing reports to improve its understanding of eltrombopag's role in these events.

Further Information

Should you require additional information about Promacta please refer to the Prescribing Information (which can also be found at http://www.promactacares.com/prescribing_information.pdf) or contact GlaxoSmithKline Medical Information via the GSK Customer Response Center at 1-888-825-5249.

GlaxoSmithKline reminds Health Care Professionals to continue to report adverse reactions to FDA MedWatch at 1-800-FDA-1088 or www.fda.gov/medwatch in accordance with the national spontaneous reporting system rules. GlaxoSmithKline encourages Health Care Professionals to continue to report suspected adverse reactions, pregnancy, overdose and unexpected benefits of PROMACTA at 1-888-825-5249.

Sincerely,

Manuel Aivado, MD
Director, Global Clinical Development Oncology
GlaxoSmithKline

5/18/10

Sources

Food and Drug Administration (FDA). Promacta (eltrombopag): Portal Venous System Thromboses in Study of Patients With Chronic Liver Disease. Public announcement. May 12, 2010.

GlaxoSmithKline. Promacta (eltrombopag): Notification of Safety Information. Dear Healthcare Professional Letter. May 4, 2010.


 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 


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