Hope for Patients with Hepatitis C
New drug combinations suppress virus
The most common form of the hepatitis C virus in the United States and worldwide — known as genotype 1 — also remains the most difficult to treat. Hepatitis C infects the liver and can lead to cirrhosis and liver cancer; an estimated 170 million people around the globe are infected. Although there is no vaccine to prevent hepatitis C, it is a potentially curable disease. A recent U-M study added to that potential with a new combination of investigational drugs that suppressed hepatitis C genotype 1 in a high percentage of patients who hadn’t responded to previous treatment.
Two antiviral agents, known as PEG-interferon alfa and ribavirin, are typically used to treat this form of hepatitis C. The U-M study, published January 19 in the New England Journal of Medicine, focused on patients with hepatitis C genotype 1 who had not responded to treatment with these drugs.
“The two recently approved hepatitis C drugs — telaprevir and boceprevir — combined with PEG-interferon alfa and ribavirin have limited success in patients who have not responded to previous treatment with PEG-interferon alfa and ribavirin,” says Anna S. Lok, M.D., the Alice Lohrman Andrews Research Professor of Hepatology, director of clinical hepatology, and lead author of the study. A new combination regimen to increase response rates in that population was the goal of the phase 2 clinical trial conducted by Lok and colleagues, including scientists from Bristol-Myers Squibb, which funded the study. Patients were given a combination of two investigational direct-acting antiviral agents (daclatasvir and asunaprevir) alone, or with PEG-interferon alfa-2a and ribavirin. All of the patients saw their hepatitis C viral load drop rapidly, Lok says.
Of the 10 patients who were given the four-drug treatment, all had sustained virologic response at the end of treatment and at 12 weeks after stopping treatment. Sustained virologic response means there is no hepatitis C virus detected in a patient’s blood after treatment is stopped, and research has shown later relapse to be rare. Four of the 11 patents who were given only the two direct-acting antiviral agents also achieved sustained virologic response.
Lok finds the high rate of sustained virologic response in patients who received the four-drug regimen “very exciting,” and although just 36 percent of patients given only the two direct-acting antiviral agents achieved sustained virologic response, Lok is encouraged by those results as well. “This is the first study to show that sustained virologic response can be achieved without the use of interferon or ribavirin,” Lok says. “These data are very encouraging because PEG-interferon alfa and ribavirin are associated with many side effects, and many patients with hepatitis C choose not to receive treatment for fear they cannot tolerate those drugs.”
The results suggest that further research into combinations of direct-acting antiviral agents should be encouraged, Lok says, but she also cautions about selecting the right combination of direct-acting antiviral agents in studies of interferon-free regimens. “In this study, all seven patients who received only two direct-acting antiviral agents and did not achieve sustained virologic response had emergence of drug resistance variants to both drugs,” she says.
Hepatitis C is transmitted through direct contact with infected blood and blood products. Up to 80 percent of those infected with hepatitis C will become chronically infected and, of those, 20 percent will develop cirrhosis. Up to 25 percent of patients with cirrhosis of the liver may progress to liver cancer. —MARY MASSON/RICK KRUPINSKI