Chronic hepatitis C
11.11.2010 17:30
Phase III studies show: Telaprevir-based combination treatment more effective than standard therapy
Treatment-naïve patients with chronic hepatitis C virus genotype 1 who received the experimental protease inhibitor telaprevir for eight or twelve weeks in addition to standard therapy were significantly more likely to achieve a sustained virological treatment response than patients receiving standard therapy alone. In patients who responded early to the therapy, the total treatment duration could also be halved without affecting the success of the therapy. These are the results of two Phase III studies recently presented at the 61st Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) in Boston. There is much to suggest that treatment options for patients with HCV infection will improve noticeably in the near future.
Around 170 million people worldwide are chronically infected with the hepatitis C virus (HCV).(1,2) In Germany, around 500,000 people are affected.(3) The chronic infection often leads to liver cirrhosis or hepatocellular carcinoma (4) and is the most common reason for liver transplants. Since no vaccination is available, drug therapy approaches that lead to virus elimination are important.
The standard treatment for hepatitis C consists of a combination of pegylated interferon and ribavirin. However, with this treatment, which lasts 48 weeks, at most one in two patients with the particularly common chronic genotype 1 HCV infection can be permanently freed from their viral load and thus cured. There is therefore an urgent need to develop optimized treatment regimens that lead to higher cure rates and thus better protect patients from HCV-related complications. At the AASLD annual meeting in Boston, study data from the two not yet approved protease inhibitors telaprevir and boceprevir were presented. The results suggest that the triple combination of pegylated interferon, ribavirin and protease inhibitors may represent an optimized therapeutic option.
ADVANCE study: response rates compared to standard therapy
The results of the placebo-controlled, double-blind phase III ADVANCE study on telaprevir showed that eight or twelve weeks of administration of the protease inhibitor in addition to standard therapy is superior to standard therapy alone. As part of the study, 1088 previously untreated patients with chronic hepatitis C (genotype 1) were randomized into three groups. One group (T8PR; n = 364) received standard therapy (180 mg pegylated interferon alfa-2a by injection once weekly and 1000 or 1200 mg oral ribavirin once daily) plus oral telaprevir (750 mg, every eight hours) for eight weeks, followed from standard therapy up to a total treatment time of 48 weeks. The second group (T12PR; n = 363) received the same medication but continued the telaprevir-based treatment regimen for 12 weeks. The third group (PR48) received standard therapy exclusively for 48 weeks. The primary endpoint of the study was the absence of detectable virus particles in the patients' blood at the end of treatment and six months thereafter. This “sustained virologic response” (SVR) is generally equated with a cure of the disease.
Result: The patient groups that received the telaprevir-based treatment regimen for eight or twelve weeks achieved SVR significantly more often than the patients who only received the standard of care (75 and 69 percent versus 44 percent, respectively). Comparably high response rates have so far not been achievable in chronic genotype 1 HCV. Prof. Ira Jacobson from the Department of Gastroenterology and Hepatology at Weill Cornell Medical College New York spoke in Boston on the occasion of the data situation about an important new therapy option that can significantly improve future care for hepatitis C.
ILLUMINATE study: treatment time in early responders
The telaprevir-based treatment regimen not only increased the clearance rates of chronic hepatitis C, but also significantly shortened the treatment time for the majority of patients. This is shown by the current data from the ILLUMINATE study. In this open-label, randomized phase III study, 540 treatment-naïve patients received the 12-week combination treatment of telaprevir, pegylated interferon and ribavirin, followed by standard therapy alone. Those patients in whom no virus was detectable in the blood after completing the three-combination treatment were identified (n = 352). 322 of them were randomly assigned to two groups: one received treatment lasting a total of 24 weeks, the other 48 weeks. The result: The proportion of patients who were virus-free six months after the end of treatment (primary endpoint of the study) hardly differed between the groups (92 versus 88 percent). Short therapy over 24 weeks was therefore not inferior to long therapy over 48 weeks - which means that for patients who respond early to treatment, the duration of therapy could be halved in the future.
Overall, the experts in Boston agreed that the telaprevir-based treatment regimen will significantly expand the therapeutic spectrum for treatment-naïve hepatitis C in the future. Another study is currently investigating whether telaprevir is also effective in previously treated patients who were unable to achieve virus elimination with standard therapy. The active ingredient telaprevir has not yet been approved in Germany.
1. WHO: Hepatitis C. 2002. On the Internet at: http://www.who.int/csr/disease/hepatitis/Hepc.pdf
2. Epidemiological Bulletin of the Robert Koch Institute; May 25, 2010 / No. 20
3. Thierfelder W, Hellenbrand W, Meisel H et al.:. Europ J Epidemiol 2001; 17: 429-435
4. Perz JF, Armstrong GL, Farrington LA et al.: J Hepatol 2006;
45(4): 529-538
November 11, 2010