Hepatitis C patients who don’t normally respond to standard treatment may have a new weapon for fighting their viral liver disease. A combination drug program, with sofosbuvir and ribavirin, has cured a majority of volunteers in a Phase II clinical trial conducted by the National Institute of Allergy and Infectious Disease (NIAID), a branch of the National Institutes of Health (NIH).

Most people with hepatitis C virus (HCV) are unaware of their infection and often carry the disease for decades before liver damage and symptoms occur. About three-quarters of the 3.2 million U.S. cases are baby boomers that have carried the disease for most of their adult lives. Doctors in New York are now required to offer hepatitis C screening for this age group.

The virus comes in several flavors, known as genotypes. Most U.S. patients have genotype 1, which is also the most difficult to treat. The standard therapy involves a complicated regimen of weekly injections of pegylated interferon-alpha, which boosts the immune system, in combination with the oral drug ribavirin and an HCV protease inhibitor, both of which block different facets of viral replication.

However, genotype 1 cases tend to be less responsive to interferon-based treatment, which is associated with severe side effects like depression and anemia.

"There is a pressing need for hepatitis C virus treatments that are less burdensome to the patient, have fewer side effects and take less time to complete,” said NIAID director and study co-author Dr. Anthony Fauci. “Building on previous work, this trial provides compelling evidence that interferon-free regimens can be safe and effective."

For this interferon-free trial, 60 patients were recruited. Each took a standard med — ribavirin — along with the experimental drug sofosbuvir for six months. Sofosbuvir has shown tremendous promise in earlier trials and is expected to earn approval from the Food and Drug Administration next year. This oral medication is manufactured by Gilead Sciences, Inc., which supplied it to the study physicians.

The first part of the trial included 10 patients, with nine being cured by the treatment. If the virus cannot be detected for a period of 12 weeks after stopping therapy, the patient is considered cured, said principal investigator Dr. Shyam Kottilil of the NIAID. Any additional screens after 24 weeks were also negative.

Next, the researchers looked at patients with severe hepatitis in two follow-up groups. Each set included 25 patients who received a unique dosage of ribavirin, but the same amount of sofosbuvir.

"Because ribavirin can cause serious side effects, including anemia, we wanted to compare response rates in patients taking low-dose ribavirin with results from patients on a weight-based dosage," said Kottilil. "We saw an overall cure rate of about 70 percent using regimens that did not include interferon."

Five out of six subject in this investigation were African Americans, who have been understudied in terms of interferon-free therapies for hepatitis C, but who suffer from more hepatitis C relative to other ethnic groups in the U.S.

"While African-Americans make up about 13 percent of the U.S. population, they represent more than 22 percent of people with chronic HCV infection and, compared to whites, have lower cure rates with traditional HCV therapy," said Kottilil, who continued that the trial’s results are encouraging, “especially considering the proportion of volunteers who had characteristics — such as being male, having HCV genotype-1 infection, being African-American and having advanced liver damage — that are recognized as predictors of poor response to treatment."

 

Source: Osinusi A, Meissner EG, Lee YJ, et al. Sofosbuvir and Ribavirin for Hepatitis C Genotype 1 in Patients With Unfavorable Treatment Characteristics. A Randomized Clinical Trial. JAMA. 2013.