Hi Rick,
Remember me? I was talking some time ago about shorting AGPH at $60 (I did not do it!!!). Well, I am a bit humbled but still think AGPH is overpriced at these levels in the crowded AIDS treatment arena (there will be 8 protease inhibitors on the market in 2 years).
But back to GILD...
I've observed many times that when secondary endpoints get discussed, primary ones are in doubt. Is it possible that GLX and BCHXF do not mention the viral load because it did not look good enough to be mentioned? Also, 66% patients with improved LFTs vs. 30% on placebo look less than exciting. The presentation at the liver meeting and not at the ICAR in Atlanta also hints at the unexciting data. I have heard some rumblings before that 3TC does not work in the asian population. It will be interesting to see the actual numbers.
GILD reported data from Phase I/II in September 1996. Here is an excerpt from their press release (from their Web site):
Phase I/II Data Summary - A total of 20 patients with chronic hepatitis B virus infection were enrolled in this double-blind,
placebo-controlled, Phase I/II study at three clinical centers in the United Kingdom. Neither the treating physicians nor the patients knew if a patient was receiving active drug or inactive placebo. A total of 15 patients received treatment with GS 840 (one 125 mg tablet) and 5 received placebo once per day for 28 days. Antiviral activity was determined by monitoring the viral load levels of hepatitis B virus using the Digene Hybrid Capture System assay to quantify HBV DNA before, during and after the treatment period.
The mean time since HBV diagnosis was four years and 25% of patients had previously failed HBV treatment with interferon-alpha. The
majority of patients enrolled in the study (65%) also tested positive for human immunodeficiency virus (HIV), the causative agent of AIDS.
During four weeks of treatment, GS 840 resulted in a statistically significant (p=0.001) mean decline in HBV DNA levels of 97 percent (1.8log) from baseline, compared with an increase of 7 percent (0.02 log) from baseline, in the placebo group. All treated patients experienced a >90 percent decrease in HBV DNA versus none of patients on placebo. Levels of HBV DNA returned to baseline between one and six weeks after the 28 days of GS 840 dosing, underscoring the antiviral effect of drug treatment. In addition, during the first eight weeks, one marker of hepatitis infection (HBe antigen) became transiently undetectable in one patient.
GS 840 treatment was well tolerated with only mild to moderate clinical events, which included moderate nausea in two patients. The
principal drug-related serum chemistry changes were transient hepatic transaminase elevations (AST or ALT >300 U/L). These elevations in
liver enzymes were observed in three patients while receiving treatment and in four patients after dosing. Similar transaminase elevations have been observed during or after treatment with other anti-HBV therapies in association with a response to HBV and eradication of chronic infection or seroconversion.
Several features support that the elevations observed in the GS 840 study were related to an immunological response. Specifically, patients with transaminase elevations during dosing also had more sustained reductions in HBV DNA. Additionally, the elevations during dosing were observed only in HIV negative patients and not in HIV positive patients. HIV positive patients may have been less able to generate an immunologic response to the viral infection".
GILD is at least 1-2 years behind GLX and BCHXF on HBV but its data looks much stronger so far. It likely will need a partner for Phase III/marketing (if the current phase II data looks good).
T. |
