GSK presents phase III results for eltrombopag in hepatitis C virus related thrombocytopenia

Full results from ENABLE 1 and initial data from ENABLE 2 presented at the 62nd Annual Meeting of the American Association for the Study of Liver Diseases

Findings from the ENABLE clinical trials, which evaluated the ability of eltrombopag to raise and maintain platelet levels in patients with chronic hepatitis C virus (HCV) infection and low platelet levels that would preclude initiation of interferon-based antiviral therapy, were presented today at the 62nd Annual Meeting of the American Association for the Study of Liver Diseases in San Francisco. Use of eltrombopag to treat thrombocytopenia in patients with chronic HCV infection is not approved anywhere in the world.

In ENABLE 1, patients who received eltrombopag along with Pegasys® (peginterferon alfa-2a) and ribavirin antiviral therapy achieved a statistically significant improvement in the primary endpoint of sustained virologic response (SVR), a clinically validated endpoint that means there is no detectable hepatitis C virus in a patient’s blood. 23% of patients in the eltrombopag group achieved SVR compared to 14% of patients receiving placebo (p=0.0064). Serious adverse events were reported in 20% of eltrombopag and 15% of placebo patients. During the entire study period death occurred in 2% of patients in the eltrombopag and 3% in the placebo group. Thromboembolic events were reported in 2% of eltrombopag patients and 2% of placebo patients. Elevations in liver enzymes were similar in both groups. Events consistent with worsening of liver function were reported in 13% of eltrombopag patients and 8% of placebo patients.

The ENABLE 1 trial enrolled 716 adults with HCV and platelet levels less than 75,000/µL into an open label eltrombopag treatment period. Those who achieved platelet levels greater than or equal to 90,000/µL were randomly assigned on a 2 to 1 basis to eltrombopag or placebo plus peginterferon alfa-2a and ribavirin.

Initial data from ENABLE 2, a randomised Phase III trial of eltrombopag plus PEG-Intron® (peginterferon alfa-2b) and ribavirin were also presented. The ENABLE 2 trial met its primary endpoint of improved SVR, with 19% of eltrombopag patients and 13% of placebo patients achieving SVR (p=0.0202). Serious adverse events were reported in 20% of eltrombopag and 15% of placebo patients. Death occurred in 4% of patients in the eltrombopag and 2% of placebo group. Thromboembolic events were reported in 4% of eltrombopag patients and less than 1% of placebo patients. Elevations in liver enzymes were similar in both groups. Events consistent with worsening of liver function were reported in 15% of eltrombopag patients and 8% placebo patients.

The ENABLE 2 trial enrolled 805 adults with HCV and platelet levels less than 75,000/µL into an open label eltrombopag treatment period and those who achieved platelet levels greater than or equal to 100,000/µL were randomly assigned on a 2 to 1 basis to eltrombopag or placebo plus peginterferon alfa-2b and ribavirin. Analyses are ongoing and full study results will be submitted for presentation at a future medical meeting.

“The ENABLE trials provide insight into a population that has generally been excluded from clinical trials because they are unable to initiate interferon therapy.” said Rafael Amado, Senior Vice President, Oncology Development “We will fully examine the efficacy and safety findings of both studies to evaluate the overall clinical benefit to these patients.”

About eltrombopag (PROMACTA®/Revolade®)

Eltrombopag is in development as a potential treatment for thrombocytopenia associated with chronic hepatitis C virus infection. It is subject to evaluation of the benefits and risk by regulatory authorities before being made available for use in this setting.

Eltrombopag, known by the brand name PROMACTA®/Revolade® is approved in 78 countries around the world as a treatment for thrombocytopenia in patients with chronic immune (idiopathic) thrombocytopenic purpura (ITP).

In Europe, Revolade® is indicated for the treatment of thrombocytopenia in splenectomised adult patients with chronic ITP who are refractory to other treatments, such as corticosteroids and immunoglobulins. Revolade may also be considered as second-line treatment for adult non‑splenectomised patients, where surgery is contraindicated.

In the United States, PROMACTA® is indicated for the treatment of thrombocytopenia in patients with chronic ITP who have had an insufficient response to corticosteroids, immunoglobulins or splenectomy.

BOXED WARNING and Important Safety Information

PROMACTA may cause hepatotoxicity. Increases in serum aminotransferase levels and bilirubin were observed. Liver chemistries must be measured before the initiation of treatment and regularly during treatment. See Full Prescribing Information for BOXED WARNING.

Because of the risk of hepatotoxicty and other risks including bone marrow reticulin formation, risk for bone marrow fibrosis, thrombotic/thromboembolic complications, recurrence of thrombocytopenia and hemorrhage risk after PROMACTA cessation, hematologic malignancies and progression of malignancies, and cataracts, PROMACTA is available only through a restricted distribution program called PROMACTA CARES.

Pegasys®(peginterferon alfa-2a) is manufactured by Roche, Ltd.

PEG-Intron®(peginterferon alfa-2b) is manufactured by Schering Corp, a subsidiary of Merck and Co, Inc.