Clinical

Telbivudine more effective than lamivudine for hepatitis B in phase III trial

Last Updated: 2005-11-15 17:30:17 -0400 (Reuters Health)

By Larry Schuster

SAN FRANCISCO (Reuters Health) - In the largest registration trial ever conducted for chronic hepatitis B infection, telbivudine was found to be more effective in viral suppression than the standard therapy, lamivudine, researchers reported this week at the annual meeting of the American Association for the Study of Liver Diseases

After 1 year of treatment in the phase III GLOBE study, involving 1,367 patients from 20 countries, the researchers found 60% of the hepatitis B e-antigen (HbeAg)-positive patients treated with telbivudine achieved undetectable levels of the hepatitis B virus, based on polymerase chain reaction (PCR) tests. In contrast, 40% of HBeAg-positive patients on lamivudine achieved undetectable levels.

In HBeAg-negative patients, telbivudine treatment reduced HBV DNA to below detectable levels in 88% of patients, compared to 71% with lamivudine treatment. In both cases, the p value was less than 0.01.

Idenix is developing telbivudine, an orally administered, once-a-day nucleoside analogue, in collaboration with Novartis Pharma AG.

In a statement, Idenix said the primary efficacy endpoint of the GLOBE study was therapeutic response, a composite endpoint coupling viral suppression (serum HBV DNA suppression below 100,000 copies/mL) with either improved liver disease markers (ALT normalization) or loss of detectable HBeAg.

In HBeAg-positive patients, therapeutic response was 75% among patients treated with telbivudine compared to 67% for patients treated with lamivudine (p < 0.05). The response after one year was similar for HBeAg-negative patients taking either treatment (75% versus 77%, respectively).

Dr. Ching-Lung Lai of the University of Hong Kong is the lead investigator of the GLOBE study. In an interview with Reuters Health, he said the rate of resistance triggered by each drug was another key difference. By one year, 2% to 3% of those on telbivudine had become resistant compared to 8% to 9% of those on lamivudine. In previous studies, lamivudine has been associated with resistance in 20% to 30% of patients.

Dr. Lai said telbivudine produces at most "trivial" side effects, while at the same time providing rapid suppression of viral load.

He said that findings from the GLOBE study show that suppression of the virus to undetectable levels at 6 months was associated with an increased likelihood of a therapeutic response at one year. A similar result was found on earlier lamivudine studies. Researchers said, though, the association was even stronger with telbivudine.

Telbivudine also shares a feature with other nucleoside analogues that have prompted warnings in other drugs in that class. The sudden withdrawal of the drug in HBeAg-negative patients can lead to serious complications, even in patients who had previously felt healthy prior to the drug's withdrawal.

The study is the first hepatitis B registration trial that included participants from mainland China, about 350, where the largest number of people with chronic hepatitis B reside. Researchers estimate that 350 million to 400 million people worldwide have chronic HBV infections. About 120 million people with chronic infections live in China, where infected people face severe employment and academic discrimination, often due to a misunderstanding about how the virus is spread.