Jul 30, 2013
The indications for eltrombopag (Revolade, GlaxoSmithKline Trading Services) should be extended to include adults with chronic hepatitis C virus (HCV) infection who have thrombocytopenia severe enough to prevent the initiation of interferon-based therapy or limit the maintenance of optimal therapy, according to a July 25 recommendation by the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA).
"Treatment with pegylated interferon and ribavirin is the current standard of care for patients with HCV, however both the European Association for the Study of the Liver guidelines and the American Association for the Study of Liver Diseases report the presence of thrombocytopenia among the relative contraindications to antiviral therapy," according to a GlaxoSmithKline statement.
"A sustained virologic response is the goal for treatment of hepatitis C infection and our clinical study, the largest ever in cirrhotic patients with low platelet counts and chronic hepatitis C infection, demonstrated that eltrombopag in combination with interferon-based therapy, allowed more cirrhotic patients with low platelet counts to reach this goal," Rafael Amado, MD, head of oncology research and development at GlaxoSmithKline said in the statement.
The committee's opinion was based on data from 2 randomized, double-blind, placebo controlled, multicenter phase 3 studies with a total of 1521 patients with platelet counts below 75000 µl, the ENABLE 1 and 2 (Eltrombopag to INitiate and Maintain Interferon Antiviral Treatment to Benefit Subjects with Hepatitis C related Liver DiseasE) trials. Patients in ENABLE 1 received peginterferon alfa-2a (Pegasys, Genentech) plus ribavirin for antiviral treatment and patients in ENABLE 2 received peginterferon alfa-2b (Pegintron, Merck) plus ribavirin.
Eltrombopag was previously approved in the European Union to treat thrombocytopenia in adult splenectomized patients with chronic immune (idiopathic) thrombocytopenic purpura (ITP) who haven't responded to other treatments including corticosteroids and immunoglobulins. It can be considered as a second-line treatment for adult nonsplenectomized patients in whom surgery is contraindicated.
Eltromopag is marketed in the US under the trade name Promacta (GlaxoSmithKline) and is approved for both indications there.
Limitations to the use of eltrombopag include:
- Eltrombopag should not be used to normalize platelet counts;
- Eltrombopag should only be used in patients with chronic HCV whose thrombocytopenia is severe enough to prevent initiation of interferon therapy or maintenance of optimal interferon therapy; and
- The safety and efficacy of eltrombopag have not been established in combination with direct-acting antiviral agents that are approved to treat chronic hepatitis C genotype 1 infection.
Eltrombopag can cause hepatotoxicity, and hepatic enzymes should be measured before beginning therapy. When used in combination with interferon-based antiviral therapy, eltrombopag can increase the risk for hepatic decompensation, so patients should be monitored closely.
Venous and arterial thrombotic and thromboembolic events have occurred in patients receiving eltrombopag, with portal vein thrombosis reported most frequently. Patients with poor baseline liver function are at increased risk and should be monitored closely.
At least 10% of patients in both trials experienced headache, anemia, decreased appetite, insomnia, cough, nausea, diarrhea, alopecia, pruritus, myalgia, pyrexia, fatigue, influenza-like illness, muscle weakness, chills, and peripheral edema.
The European public assessment report (EPAR) will be revised to include the updated summary of product characteristics (SmPC) after the European Commission grants marketing authorization for this indication.
The European Commission generally follows the recommendations of the CHMP and usually delivers its final decision within 3 months of the CHMP recommendation.
European Medicines Agency statement, July 25, 2013. Overview