HBV Drug LdT: 2 years followup
Phase IIb Extended-Treatment Trial of Telbivudine (LdT) vs. Lamivudine vs. Combination Treatment in Hepatitis B Patients: Two-Year Results
Reported by Jules Levin
C.L. Lai, N. Leung, E.K. Teo, M. Tong, F. Wong, H.W. Hann, S. Han, T. Poynard, X.J. Qiao, K. Pietropaolo, D. Lloyd, N. Brown (Idenix Pharmaceuticals)
Lai & colleagues presented at DDW (May 2005) this two year data on LdT (telbivudine), a new drug for hepatitis B therapy.
--The combination of LdT+LAM provided no efficacy advanatage compared to LdT.
--HBV DNA (viral load) reduction after 2 yrs was -5.4 log for patients receiving LdT vs -3.9 log for patients receiving lamivudine (3TC).
--ALT normalization after 2 yrs was 81% (LdT) vs 47% (LAM).
--trend towards better HBeAg seroconversion for LdT: 38% vs 22%
--Percent of patients PCR negative after 2 yrs favored LdT: 71% vs 32%
--there was an association between viral load reduction (HBV DNA) after 6 months
& outcomes at 2 yrs. Patients with <1000 copies/ml at 6 months were more likely to be PCR negative, normalize ALT, have HBeAg seroconversion, & less likely to have treatment failure.
--phase III studies are ongoing.
In this phase IIb study patients received for year 1 lamivudine (3TC) 100 mg/day or LDT at a dose of 400 or 600 mg/day, or LdT 400mg+LAM 100mg or LdT 600mg+LAM 100mg. In the second year of this study patients who had recd LAM continued receiving LAM. Patients receiving LdT 400 or 600mg now received LdT 600mg. Patients on combination therapy in year 1 now received LdT 600+LAM 100. The study will go for 3 years in total.
All 104 patients enrolled were HBeAg+ & HBsAg+ at screening.
Mean age: 37 (18-68)
Mean weight: 69.8 kg (42.0-119.8)
Median HBV DNA (viral load): 8.89 to 9.66 logs
Median ALT: 122-152 IU/L (32-1657)
19-22 patients in each study arm
SERUM HBV DNA MEAN DECREASE:
In patients receiving only LdT: -5.4 log (n=44)
Lamivudine (n=19): -3.9 log
LdT+LAM (n=41): -5.4 log
HBV DNA NEGATIVE by PCR:
Serum HBV DNA never below 100,000 copies/ml (AASLD recommended level of suppression)
*p<0.05 vs lamivudine
EARLY VIRAL SUPPRESSION PREDICTED OUTCOMES
Previously study investigators reported that the first-year efficacy outcomes were best for patients with the lowest viral load after the first 6 months (Lai et al, Gastroenterology in press).
To assess the relationship between viral response at 6 months & longer term outcomes, data from all patients at 2 yrs were pooled, regardless of treatment. Patients were categorized according to serum HBV DNA levels after 6 months of treatment: >1000 vs <1000 copies/ml.
After 2 yrs therapy in study, patients with <1000 copies/ml at week 24 did best after 2 yrs in percent PCR negative (86% vs 23%); ALT normalization (85% vs 51%); HBeAg seroconversion (41% vs 15%); & treatment failure (2% vs 17%).
Patients with HBV DNA <1000 copies/ml at 6 months: