An international clinical trial investigating the efficacy and safety of a combination oral therapy in hepatitis C patients with liver cirrhosis resulted in over 90% of patients being cleared of hepatitis C virus infection after 12 weeks of treatment. The results have been published in the New England Journal of Medicine.
Hepatitis C is a liver disease caused by hepatitis C virus (HCV), which is transmitted predominantly via infected blood. Common routes of exposure are therefore sharing needles with infected individuals to inject drugs, and mother-to-child transmission before or during birth. Sexual transmission is possible, although it is not common. The main cells targeted for viral replication are liver cells called hepatocytes, and infection often results in chronic hepatitis (inflammation of the liver), liver cirrhosis (replacement of liver tissue by scar tissue) and liver cancer. It is estimated that 184 million people worldwide are infected with HCV; 25% of which have cirrhosis in the US.
HCV infection can be treated successfully in some individuals using a type of therapy involving interferon-containing treatments, but they are associated with toxic effects in those with cirrhosis and cannot be used in many due to the risk of severe complications and even death. There has therefore been a need to develop interferon-free treatments to increase the safety and effectiveness of therapy in HCV infected individuals with cirrhosis.
The treatment used in this phase 3 clinical trial, which was called TURQUOISE-II, was a combination therapy involving several different drugs targeting different parts of the virus. 380 patients were enrolled in the trial which took place across 78 sites in North America and Europe. Patients had cirrhosis and chronic HCV infection with genotype 1, which is one of 7 genotypes that HCV can be classified into. The patients were randomly assigned to receive the combination treatment for either 12 or 24 weeks, and at the end of the trial the amount of virus remaining in the body was investigated.
The response of patients was investigated twelve weeks after the last dose was received, and of the patients that received therapy for 12 weeks almost 92% had no detectable virus in the blood. Almost 96% of patients receiving therapy for 24 weeks were also found to have an undetectable viral load.
“These are out-of-the-ballpark response rates, not on the same planet as interferon,” said Dr Fred Poordad, vice president of the Texas Liver Institute in San Antonio and lead author of the study in a press release. “Patients with advanced liver disease can now be cured of their hepatitis with a very well-tolerated and short regimen,” he added.
Although this study is very exciting, it did not investigate whether cirrhosis was reversed or if the likelihood of developing liver cancer was decreased. According to Charles Gore, chief executive at the Hepatitis C Trust, although this study was limited to genotype 1, treatments for genotypes 2 and 3 were “close behind.”
It is hoped that this treatment will reach markets by the end of this year, or early 2015, and has been hailed a major breakthrough by experts.