icon_folder.gif   Conference Reports for NATAP  
  AASLD ( American Association for the Study of Liver Diseases)
November 9-13, 2001, Dallas
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New Hepatitis B Drugs
Written by Jules Levin
  Entecavir vs 3TC Resistance
A more detailed report is forthcoming but here are a few highlights from this meeting. several apparently promisingly drugs for treating HBV are in human development and moving along and had data presented on them here at AASLD: LDT, FTC (not good for 3TC resistance), adefovir, and entecavir. This morning data was presented on entecavir in 3TC resistant patients. Previous study data showed 0.5 mg (highest of 3 doses) dose of ETV reduced viral load by over 4 log in treatment-naive at week 20. The data this morning was presented in oral session. 85% reportedly had YMDD mutation. Three ETV doses were used: 0.1mg, 0.5mg and 1.0mg. Mean HBV DNA was about 9 log. About 40 patients in each arm. 79% in the high dose arm (1.0 mg) had undetectable HBV-DNA at week 24 by bDNA, and a 4.4 log reduction in HBV-DNA. By PCR 17% had undetectable HBV-DNA. 93% had 2 or more log reduction. There was a dose response. The group receiving 3TC 100mg had little HBV-DNA response. 11% in the high dose group (n=27) had loss of HBeAg compared to 6% in the 3TC continuation arm. There were 67 adverse events in the ETV 1.0 mg arm: headache (19), fatigue (5), abdominal pain (10), rhinitis (7). 5 discontinued and 5 had serious AE. The incidence of AEs was not different than in the 3TC arm. Although there were 2 serious AEs in the 3Tc arm. Several patients had elevated ALT.
This morning an oral talk was presented on a study for adefovir (ADV) for patients with HBeAg+ chronic HBV. This study looked at changes in liver histology. This 48+ week study looks at fibrosis, Knodell score, and necroinflammation. HBV-DNA was 8.4 log at baseline ALT 95. About 20% were nonresponders to IFN and <1%-3% had prior 3TC. Median Knodell scores were about the same in placebo 10mg and 30mg ADV arms: 9.5-10.0, necroinflammation 7.0-8.0, fibrosis 1.0. Cirrhosis: 4% in 30mg arm, 7% in 10mg arm, 8% in placebo. The 10 and 30 mg arms had about the same response measured by Knoedell (Histology): 53-59% showed improvement compared to 25% in placebo arm. 28%-36% showed no improvement in ADV arms compared to 65% in placebo arm. 10-12% of patients across the 3 arms had missing data. The difference between ADV 10 mg and placebo was significant (p<0.001). Necroinflammation: similar results--71-77% showed improvement in ADV arms vs 41% in placebo; 12-15% in ADV arms showed no imprivement compared to 26% in placebo. 34% in placebo showed worsening compared to 10-13% in ADV arms. Fibrosis: 41% showed improvement in 10mg ADV arm, 54% in ADV 30mg arm, and 26% in placebo. 26% worsened in placebo while 14% worsened in 10mg arm and 19% in 30mg arm. 50% remained the same in placebo vs 45% in 10mg and 37% in 30 mg arm. HBV-DNA: reduced by median 3.52 log in 10 mg arm (n=172) (21% <400 copies/ml HBV-DNA), 4.76 in 30 mg arm (n=173) (39% <400 HBV-DNA) and .55 in placebo (0%). 14% HBeAg seroconverted in 30mg arm, 12% in 10mg arm, and 6% in placebo. 33% exp erienced HBeAg loss in 30mg arm, 23% in 10mg arm, 17% in placebo. Serious AEs, AEs, and discontinuations were about the same in all 3 arms (5% serious AE, 87-95% AE, 7-8% disct. Dose reduction was 25% in 30mg ADV arm vs 3% in 10mg arm. 8% in 30 mg arm had confirmed increase 0.5 or more serum creatinine increase from baseline. No serum phosphorous confirmed decreases <1.5 mg/dL in any arm. Resistance reported later in conference. ADV 10 mg selected for development due to renal lab abnormalities with 30mg dose.
Data on FTC is also being presented showing viral load reductions. Maureen Myers reported median HBV-DNA reduction of 3.63 log at week 4 using highest dose og 400mg per day. In lower doses 2-3 log reductions seen. She reported no serious adverse events, toxicities.
It seems apparent that combination therapy for HBV should be the approach.