New drug helps hepatitis C patients start antiviral therapy

DURHAM, N.C. -- A new drug that stimulates the production of blood platelets can enable patients infected with hepatitis C virus to take other antiviral medications they previously could not take to fight the disease, according to the results of a clinical trial led by a Duke University Medical Center researcher.

Hepatitis C attacks the liver. An estimated 20 percent of patients go on to develop cirrhosis, a condition that involves destruction of liver cells.

Patients with hepatitis C who have cirrhosis and abnormally low platelet levels, a disorder known as thrombocytopenia, cannot take the standard drugs for fighting the infection, because these drugs also act to lower platelet counts further. Patients with low platelet counts are also at risk for spontaneous bruising; bleeding in mucosal linings, such as in nose, gums and the gastrointestinal tract; and in severe cases, bleeding in the brain. They are also at greater risk of bleeding at the time of medical procedures.

The new drug, called eltrombopag, works by stimulating cells in the bone marrow to produce more platelets, according to Duke liver specialist John McHutchison, M.D., professor of medicine and the principal investigator for the clinical trial. The trial was of a type called Phase II, which tests the safety and effectiveness of a drug in a small population.

McHutchison presented the results of the trial on Monday, Oct. 30, 2006, at the annual meeting of the American Association for the Study of Liver Disease, in Boston. The trial was supported by GlaxoSmithKline, which developed eltrombopag. McHutchison has received research support from GSK.

To date, physicians have been reluctant to prescribe the standard antihepatitis C drugs called pegylated interferon and ribavirin to patients with advanced liver disease due to hepatitis C and thrombocytopenia because of pegylated interferon's known effect on lowering platelet counts in the blood, McHutchison said.

"When we give these antiviral agents to patients with normal platelet counts, we can cure approximately half of them," McHutchison said. "Eltrombopag increases platelet levels to the point where patients with thrombocytopenia can then be effectively treated with the antiviral therapies. If the promising results we've seen so far in these early clinical trials are borne out in future larger scale registration trials, we will be able to potentially treat many more patients for whom there are currently no options."

The trial enrolled 74 hepatitis C patients with thrombocytopenia. They were randomized to one of four groups: three groups received eltrombopag at doses of 30 milligrams, 50 milligrams or 75 milligrams, and one group received an inactive placebo. All of the patients took the drug daily for four weeks. Patients whose platelet counts rose to a predefined level after four weeks were then started on the standard antiviral treatment.

"We found that 95 percent of the patients who received the highest dose of the new drug responded with increased levels of platelets, and 91 percent of those patients were then able to start antiviral therapy with pegylated interferon and ribavirin," McHutchison said. "After 12 weeks, 61 percent of these patients were still able to maintain antiviral therapy."

The patients receiving the lower doses of the drug also had better responses than those receiving placebo. Three-quarters of the patients taking either 30 milligrams or 50 milligrams of the drug demonstrated increased platelet levels enough to initiate antiviral therapy. In the placebo group, no patients saw this improvement. Fifty-three percent of patients taking the 50 milligram dose were able to complete the 12-week course of antivirals, and 36 percent of those taking 30 milligrams completed the course.

Side effects of the drug -- headache, dry mouth, nausea and diarrhea -- were not clinically worrisome, McHutchison said.

The new drug also may benefit patients who have low platelet counts caused by other liver diseases, particularly those who need to undergo surgery or other invasive procedures that carry a significant risk of bleeding, he said.

McHutchison and other investigators are currently involved in planning larger Phase III clinical trials of eltrombopag to further refine the optimal dosing for the drug and to determine which patients would benefit most from receiving the drug. Phase III trials usually are the final stage before a new drug is introduced to the marketplace.

It is estimated that about 3.9 million Americans are infected with the hepatitis C virus. The virus is most commonly transmitted by injected drug use.

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