Drug & Device Development

Entecavir bests lamivudine for treatment of chronic hepatitis B

Last Updated: 2006-03-08 17:00:15 -0400 (Reuters Health)

NEW YORK (Reuters Health) - Entecavir appears to be more effective than lamivudine for the treatment of hepatitis B e antigen (HBeAg)-negative and HBeAg-positive chronic hepatitis B (HBV) during 1 year of treatment, according to two phase III trials reported in the March 9th issue of the New England Journal of Medicine.

However, entecavir (Baraclude, Bristol-Myers Squibb) is considerably more expensive, Dr. Jay H. Hoofnagle notes in an accompanying editorial, and its safety over the long-term has yet to be established.

Entecavir is a selective guanosine analogue that inhibits HBV DNA polymerase, Dr. Ting-Tsung Chang from National Cheng Kung University Hospital in Tainan, Taiwan, and his co-authors explain.

They enrolled patients with HBeAg-positive hepatitis B who had not previously been treated with a nucleoside analogue. Patients were randomly assigned to entecavir 0.5 mg once daily (n = 354) or lamivudine (Epivir-HBV, GlaxoSmithKline) 100 mg once daily (n = 355).

At 48 weeks, entecavir was associated with a higher rate of histologic improvement (72% versus 62%, p = 0.009) and alanine aminotransferase level normalization (68% versus 60%, p = 0.02). HBV DNA fell to undetectable levels in 67% of entecavir-treated patients and in 36% of those on lamivudine (p < 0.001).

"The improved histologic benefit of entecavir as compared with lamivudine and its greater effect on viral suppression suggest that with long-term treatment, entecavir might also reduce the risk of end-stage liver disease and hepatocellular carcinoma," Dr. Chang and the team write.

Meanwhile, Dr. Ching-Lung Lai, from Queen Mary Hospital in Hong Kong, and colleagues performed a similar study among patients with HBeAg-negative hepatitis B, with 325 randomized to entecavir and 313 to lamivudine.

At 48 weeks, histologic improvement (70% versus 61%, p = 0.01) and alanine aminotransferase level normalization (78% versus 71%, p = 0.045) favored entecavir. Undetectable HBV DNA levels were achieved in 90% of those on entecavir and 72% of those on lamivudine.

In both studies, the adverse event profiles were similar in the two treatment groups, and the authors observed no evidence of viral resistance to entecavir. The two research teams note that continued surveillance will be required to confirm entecavir's long-term safety.

The researchers conclude that entecavir can be considered as primary therapy for patients with HBeAg-negative and HBeAg-positive chronic hepatitis B not previously treated with a nucleoside analogue.

In his editorial, Dr. Hoofnagle, from the National Institute of Diabetes and Digestive and Kidney Diseases in Bethesda, Maryland, notes that entecavir, like other antiviral agents, "is easy to start but difficult to stop" because of the risk of relapse and severe exacerbation once the drug is stopped.

He suggests that either adefovir or entecavir would be appropriate first-line agents, but that treatment should not be based on HBV DNA levels alone, but instead should be started if active disease is present.

N Engl J Med 2006;354:1001-1020,1074-1075.