GlaxoSmithKline initiates trials of Promacta®/Revolade™ (eltrombopag) to investigate the potential to aid hepatitis C patients in achieving sustained virological response

GlaxoSmithKline (GSK) today announced the commencement of two parallel Phase III studies to assess the clinical benefits of its investigational compound PROMACTA®/REVOLADE™ (eltrombopag)in hepatitis C-associated thrombocytopenia, a condition characterised by decreased platelet counts. The studies, ENABLE 1 and ENABLE 2 (Eltrombopag to INitiate and Maintain Interferon Antiviral Treatment to Benefit Subjects with Hepatitis C related Liver DiseasE), will measure the ability of eltrombopag to raise platelet counts sufficiently enough to enable the initiation of antiviral therapy and to allow sustained antiviral therapy in thrombocytopenic hepatitis C patients. The clinical benefit of eltrombopag will be measured by the proportion of subjects who are able to achieve sustained virological response (SVR).

SVR is defined as an undetectable viral load of hepatitis C for a period of six months post-treatment and is the desired outcome of antiviral therapy. SVR is a determination that the hepatitis C virus is no longer replicating — a status that is viewed clinically to be an eradication of the virus and a decreased risk of disease progression.[1]

“The launch of both ENABLE trials is of great interest to many investigators in the field,” said John McHutchison, MD, Professor of Medicine and Associate Director, Duke Clinical Research Institute, Durham, North Carolina, US. “Thrombocytopenia is a complicating factor in hepatitis C treatment. Not only can it interfere with the administration of effective doses of antiviral therapy, but in some cases treatment may be terminated or not started at all. In a previous Phase II study, eltrombopag, compared to placebo, increased platelet counts and allowed more patients to complete the first 12 weeks of antiviral therapy, giving them an opportunity to achieve an SVR. ENABLE will investigate the effect of eltrombopag over a 12-month treatment period to determine how it may help patients to achieve SVR, which in clinical terms is considered a cure for hepatitis C, as well as better understand any related toxicities or tolerability issues.”

Thrombocytopenia in patients with chronic hepatitis C virus (HCV) can occur as a result of damage to liver cells that produce thrombopoietin (the body’s natural platelet growth factor), or due to disease progression from cirrhosis. It may also occur as a consequence of antiviral (interferon) therapy used to treat HCV infection.[2],[3]

Combination antiviral treatment (peginterferon plus ribavirin) is the standard regimen used to control HCV infection.i This approach is critical for successful management of HCV and provides patients with the potential for a cure.

Eltrombopag is an investigational oral, non-peptide platelet growth factor. The ENABLE trials will investigate if eltrombopag will allow patients a greater opportunity to maximize the dose and duration of their antiviral therapy, thus improving the likelihood of achieving SVR. The ability to achieve and maintain SVR not only provides patients with clinical benefits, but is also shown to have a positive impact on quality of life with significant improvements in perceived wellness, vitality, social functioning and health distress.[4]

In addition, a Phase II subgroup analysis evaluating eltrombopag in hepatitis C patients will be presented at the forthcoming 58th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) in Boston, Massachusetts.[5]