New Drug May Help Increase Platelet Counts in Patients With Hepatitis C

Laurie Barclay, MD

November 28, 2007 — Eltrombopag (Promacta, Revolade; GlaxoSmithKline) may help increase platelet counts in patients with hepatitis C virus (HCV) infection, thereby enabling them to take antiviral drugs, according to the results of a randomized controlled trial reported in the November 29 issue of the New England Journal of Medicine. This new, orally active thrombopoietin-receptor agonist also increased platelet counts in patients with idiopathic thrombocytopenic purpura.
"We feel this is an important development for many people infected with [HCV] worldwide," lead author John G. McHutchison, MD, from the Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina, says in a news release. "A significant number of patients with HCV infection will at some point develop platelet problems that will compromise their getting the best treatments we have. Anything we can do to prevent that from happening would improve their care."
In this phase 2, multicenter trial, 74 patients with cirrhosis caused by HCV and with platelet counts between 20,000 and 70,000/mm3 were randomly assigned to receive either eltrombopag (30, 50, or 75 mg) or placebo daily for 4 weeks. The main efficacy outcome measure was a platelet count of 100,000/mm3 or more at week 4. Eltrombopag or placebo were continued for 12 additional weeks, and peginterferon and ribavirin could be started at week 4.
At week 4, platelet counts were increased to 100,000/mm3 or more in none of the 17 patients receiving placebo. However, in patients with available data, eltrombopag was associated with platelet increases in a dose-dependent manner. Platelet counts of 100,000/mm3 occurred in 9 (75%) of 12 patients receiving a 30-mg dose of eltrombopag daily, in 15 (79%) of 19 receiving a 50-mg dose, and in 20 (95%) of 21 receiving a 75-mg dose (P < .001).
During continued administration of eltrombopag or placebo, antiviral therapy was started in 49 patients, with 4 of 18 patients receiving placebo, 10 of 14 receiving 30 mg eltrombopag, 14 of 19 receiving 50 mg eltrombopag, and 21 of 23 receiving 75 mg eltrombopag. Twelve weeks of antiviral therapy were completed by 36%, 53%, and 65% of patients receiving 30, 50, and 75 mg of eltrombopag, respectively, and by 6% of patients in the placebo group, while administration of eltrombopag or placebo was ongoing.
"We are encouraged by these results and are already working on another multicenter, international, phase 3 trial where we hope these results will be confirmed," Dr. McHutchison said.
Headache was the most frequently reported adverse event during the first 4 weeks of the study. Other adverse effects were dry mouth, abdominal pain, and nausea. During the last 8 weeks of the study, reported adverse events were those typically associated with interferon-based therapy.
Study limitations were small sample size and insufficient power to determine whether adverse events were dose-related.
"Eltrombopag therapy increases platelet counts in patients with thrombocytopenia due to HCV-related cirrhosis, thereby permitting the initiation of antiviral therapy," the authors concluded. "These results require confirmation in phase 3 trials involving standard-duration courses of peginterferon and ribavirin."
GlaxoSmithKline supported this study, employs 4 of its authors, and has various financial arrangements with some other authors. Some of the authors report various financial arrangements with Roche and/or Schering-Plough.
N Engl J Med. 2007;357:2227–2236.