BOSTON — Telbivudine showed greater efficacy than lamivudine did during 2 years of treatment for chronic hepatitis B infection, according to the most recent results from the international GLOBE trial.
In the phase III trial, telbivudine (Tyzeka), which recently received Food and Drug Administration approval for the treatment of hepatitis B virus (HBV) infection, surpassed the older antiviral on all key measures of virologic and clinical efficacy.
These results were found in both HBV e-antigen (HBeAg)-positive and HBeAg-negative patients enrolled in the study of 1,367 patients, Dr. Ching-Lung Lai said at the annual meeting of the American Association for the Study of Liver Diseases.
The international, multicenter investigation was partially funded by Idenix Pharmaceuticals, the manufacturer—with Novartis Pharma AG—of telbivudine. The trial was designed to compare the efficacy of telbivudine at 600 mg/day to that of lamivudine (Epivir) at 100 mg/day in patients who were HB s-antigen positive at enrollment and had baseline HBV DNA greater than 6 log10 copies/mL, alanine aminotransferase (ALT) levels between 1.3 and 10 times the upper limit of normal, and compensated liver disease.
The study's primary efficacy end point was therapeutic response, based on a combination of viral suppression (serum HBV DNA below 100,000 copies/mL) and either improved liver disease markers (ALT normalization) or loss of detectable HBeAg.
The first-year results from the trial, presented last year, “demonstrated that telbivudine was superior to lamivudine on all measures of direct antiviral efficacy and on several key clinical efficacy measures,” said Dr. Lai, professor of medicine and hepatology at the University of Hong Kong. “The new data indicate the efficacy levels were sustained over 104 weeks.”
After 2 years of treatment, analysis showed that HBeAG-positive and -negative patients randomized to telbivudine therapy had significantly greater HBV DNA reductions (-5.7 log10 and -5.0 log10, respectively) than did HBeAG-positive and -negative patients on lamivudine (-4.4 log10 and -4.2 log10, respectively).
Similarly, significantly more patients receiving telbivudine achieved clearance of detectable HBV DNA. In HBeAg-positive patients, “telbivudine treatment led to loss of detectable HBV DNA in 56% of patients, compared to 39% with lamivudine,” said Dr. Lai. Among HBeAg-negative patients, 82% of telbivudine patients achieved undetectable HBV DNA levels, compared with 57% of lamivudine patients, he said.
Patients who had achieved HBV DNA clearance by study week 24 had the best overall response rates in terms of seroconversion, ALT normalization, and reduced therapeutic resistance, Dr. Lai noted.
Treatment failure was significantly less common with telbivudine than with lamivudine in both HBeAg-positive and -negative patients. Among HBeAg-positive patients, antiviral treatment failed in 4% of telbivudine patients, compared with 12% of lamivudine patients. In HBeAg-negative patients, there were no treatment failures in telbivudine patients, compared with 3% of patients taking lamivudine, he said.
Drug resistance occurred in 17.8% of HBeAg-positive patients on telbivudine and 30.1% of HBeAg-positive lamivudine patients during the 2-year study period; resistance was defined in the GLOBE study as HBV DNA return to greater than 5 log10 or to within 1 log10 of baseline. Among the HBeAg-negative patients, 7.3% of those on telbivudine and 16.6% of those on lamivudine developed resistance, Dr. Lai said.
Viral resistance, defined as rebound of HBV DNA after initial suppression to 1 log10 increase above nadir, was found in 21.6% of telbivudine patients and 35.0% of lamivudine patients in the HBeAg-positive group, as well as 8.6% of telbivudine patients and 21.9% of lamivudine patients in the HBeAg-negative group, he said.
Telbivudine was associated with fewer and less severe resistance-associated elevations of serum ALT levels, which occurred in 2.8% of patients, compared with 8.4% of the lamivudine group, Dr. Lai reported.
Both study drugs were generally well tolerated and had similar patterns of clinical adverse events, Dr. Lai said. Grade 3/4 creatine kinase elevations were more commonly associated with telbivudine, occurring in 13% of patients, compared with 4% of lamivudine patients, he noted.
Dr. Lai said he is a scientific adviser to Idenix Pharmaceuticals.