Hepatitis C virus free even without interferon

Hepatitis C: virus-free even without interferon
(16.10.2010) New therapy for the treatment of hepatitis C successfully tested. According to a now of „The Lancet“ Published study, the oral direct-acting experimental drug combination of two new drugs, the viral load within two weeks significantly lower - sometimes even below the detection limit.

170 million suffer from hepatitis C
More than 170 million people worldwide suffer from hepatitis C according to experts. The infectious disease caused by the hepatitis C virus (HCV) is characterized by a particularly high rate of chronic disease progression (up to 80%), which often leads to severe liver damage such as liver cirrhosis and hepatocellular carcinoma. The standard therapy is still based on a combination of drugs derived from interferon-alpha with the nonspecific antiviral „ribavirin“. The therapy with the conventional preparations, however, takes a long time (24-48 weeks) and has considerable side effects. In addition, the treatment is successful only in about 50 percent of patients. Thus, the development of new direct-acting antiviral drugs has long been the focus of hepatitis C research.

New preparations in development
So far, the development of specific drugs has progressed very slowly. As commentary in the context of „The Lancet“-However, David Thomas from the Johns Hopkins School of Medicine, Baltimore, explains that there are currently five different drug classes in clinical development. Already next year could accordingly „telaprevir“ and „boceprevir“, Two protease inhibitors are the first to be introduced. Both drugs, according to the authors of the paper, in combination with a pegylated interferon, have caused sustained viral suppression in up to 75 percent of patients. The active ingredients were also successful in genotype 1 hepatitis C, which is generally more difficult to treat and in which standard therapies often fail.

combination of „RG7128“ and „danoprevir“
In addition, according to the article first study results for the combined use of drugs „RG7128“ and „danoprevir“ in front. The polymerase inhibitor blocks „RG7128“ the synthesis of new HCV RNA and „danoprevir“ hampers as a protease inhibitor the production of virus components. Both drugs are available orally and have now been evaluated in a first dose-finding study in 88 genotype 1 patients. 74 subjects received combination therapy with different doses of the two drugs and 14 received placebo. For thirteen days, patients underwent appropriate treatment. At the beginning of the study period, as well as regularly during the 13 days and at the end of the test phase, the changes in HCV RNA concentrations (viral load in the blood) were measured to check how the virus concentration had changed in the course of the therapy. Among the subjects were never previously treated individuals as well as hepatitis C who had failed standard interferon-based therapy.

Combination therapy surprisingly successful
The scientists were able to determine that the never previously treated patients receiving the highest dose of the two drugs (1000 milligrams twice a day „RG7128“ as well as 900 milligrams „danoprevir“) had a mean reduction in HCV RNA concentration of 5.1 log10 IU per milliliter after 14 days. Patients who did not respond to prior standard therapy showed a reduction in viral load of 4.9 log10 IU per milliliter at the same dose. When using placebo, there was an insignificant increase in viral load of 0.079 log10 IU per milliliter. In some cases, the virus concentration in the patients even dropped below the detection limit.

New treatment without significant side effects
Co-author Edward Gane of the New Zealand Liver Unit in Auckland emphasized that these are amazingly good results. In addition, the combination of the preparations „RG7128“ and „danoprevir“ there „generally tolerated well, and did not involve any therapy-related serious side effects and safety-related interruptions of therapy“ explain the authors in the context of „Lancet“-Article. Also, in contrast to the rapid development of resistance in some classes of direct-acting antiviral monotherapeutic drugs used, there was no evidence of resistance to therapy. "The combination of RG7128 and danoprevir should be further developed and could be a viable interferon-free oral measure for patients with chronic HCV infection," the authors conclude. However, it is too early for a final assessment, as the Sustained Virologic Response (SVR) criterion requires that patients remain virus-free at least 24 weeks after the end of therapy.

Most of the infected do not suspect the disease
The commentator of the „Lancet“, David Thomas, however, pointed out that even a 100 percent effective therapy would not cure many infected persons “only a small proportion of the estimated 170 million people with chronic hepatitis C infection even know that they are infected; and even less start treatment.“ Thomas adds, however, that „if the interferon-sparing therapy is safer, more effective, and easier to administer (...) such an approach (s) will significantly extend trials, treatment intakes, and treatment effects“ could. Thomas compares this to the massive expansion of HIV testing and treatment that has been used after the development of highly active antiretroviral therapies. (Fp)