Reuters Health Information (2005-11-15): Telbivudine more effective than lamivudine for hepatitis B in phase III trial
Telbivudine more effective than lamivudine for hepatitis B in phase III trial
Last Updated: 2005-11-15 17:30:17 -0400 (Reuters Health)
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
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%,
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%
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