Hepatitis B - telbivudine
Hepatitis B is a serious disease caused by a virus that attacks the liver, and in extreme cases, patients can suffer from fulminant hepatic failure, in which case liver transplantation can be life-saving.
Hepatitis B is a serious disease caused by a virus that attacks the liver, and in extreme cases, patients can suffer from fulminant hepatic failure, in which case liver transplantation can be life-saving.
Chronic hepatitis B sufferers may have minimal liver disease and no complications, but some will go on to develop cirrhosis, and they have an increased risk of developing liver cancer.
The disease can be prevented by vaccination, but once the infection has taken hold, drug treatment is the only option. The first drugs to be licensed to treat hepatitis B were interferons, but these are expensive and have to be given by injection. More recently, some of the antiviral agents used to treat HIV infection, such as lamivudine and adefovir, have been used.
A new antiviral being investigated as a potential treatment for hepatitis B is telbivudine, discovered by Idenix and licensed to Novartis. A placebo-controlled dose escalation Phase I trial has been carried out to look at its safety, antiviral activity and pharmacokinetics.1 A total of 43 patients with hepatitis B e antigen positive chronic hepatitis B were given 25, 50, 100, 200, 400 or 800mg/day of telbivudine. Treatment was given for four weeks, followed by 12 weeks' follow-up. It was well tolerated at all levels, and marked dose-related antiviral activity was evident. The activity was at a maximum at doses of 400 or 800mg/day, and post-treatment return of viral load was slowest in these high dose groups. Viral dynamic analyses suggested a high degree of efficiency of inhibition of viral replication by telbivudine.
A randomised double blind Phase IIb trial has also been carried out to compare the safety and antiviral effectiveness of telbivudine alone and in combination with lamivudine.2
A total of 104 patients with chronic hepatitis B were given daily doses of 400 or 600mg telbivudine either alone or in combination with 100mg lamivudine, or the standard therapy of 100mg lamivudine. Treatment continued for a year, and the mean reduction in serum viral levels was greater in those whose treatment included telbivudine. The proportion of patients who achieved liver disease normalisation was greatest - 86% - in those given telbivudine as monotherapy than those given combination (78%) or standard lamivudine therapy (63%).