39th ICAAC Program On-Line (Results reflect the drug being given to test subject before the virus is given to them, in this case mice, however I believe it likely any Phase2 testing is the same, medicating prior to infection (6 hrs) clearly is not like anything that would be found in a clinical environment, and bolsters the governments statisticans case that the 1-2 day potential effect of NA inhibitors is not born out by clinical effects. Note when the treatment is delayed to 60 hours post infection the results are not compared to contemporary drugs, and the results are not quantified, and results are only given at maximum dosage. These is the actual data that will be presented in the conference. These results are very premature, and I expect at least 2 years at best before the FDA would even evaluate this compound given a perfect set of Phase3 trials if those test are approved for a go ahead.
wolff
Session: Novel Antiviral Agents Location: Exhibit Hall
Session Date: Monday, 9/27/99
Session Time: 11:00 am - 12:30 pm
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Effect of the Orally Administered Neuraminidase Inhibitor RWJ-270201 (BCX-1812) on Influenza Virus Infections in Mice
R.W. Sidwell1, J.H. Huffman1, K.W. Bailey1, P.A. Bemis1, T. Coogan2, K. Bush2, Y.S. Babu3
1Inst. for Antiviral Res., Utah State Univ.: Logan, UT; 2The RW Johnson Pharm. Res. Inst.: Raritan, NJ; 3BioCryst Pharmaceuticals, Inc.: Birmingham, AL
The cyclopentane neuraminidase inhibitor BCX-1812 (RWJ-270201) was evaluated against influenza virus infections in mice. In certain studies, the activity was compared to GS4104, the ethylester prodrug of the neuraminidase inhibitor GS4071. Treatment was by oral gavage (p.o.) twice daily for 5 days beginning 4 h pre-virus exposure. Against influenza A/Shangdong/09/93 (H3N2) infection, RWJ-270201 and GS4104 doses as low as 10 mg/kg/day significantly prevented deaths; lung consolidation and lung virus titers were inhibited on day 6 to a greater extent by RWJ-270201 at this dosage, and decline in arterial oxygen saturation was inhibited by doses down to 1 mg/kg/day. Against a lethal infection with influenza B/Hong Kong/5/72 virus, RWJ-270201 significantly inhibited deaths, lung consolidation and SaO2 decline at dosages down to 1 mg/kg/day; GS4104 treatment was less effective at both 10 and 1 mg/kg/day, with only lung consolidation and SaO2 decline significantly inhibited and mean day to death prolonged.
RWJ-270201 alone was evaluated against a lethal influenza A/Bayern/07/95 (H1N1) virus infection, with efficacy seen down to 1 mg/kg/day. Delay of twice daily RWJ-270201 p.o. therapy to 60 h post-virus exposure in mice infected with influenza A/NWS/33 (H1N1) virus prevented deaths of the animals using a dose of 10 mg/kg/day. No toxicity was seen in any experiment, the highest dose used being 100 mg/kg/day. No acute toxicity has been observed in mice or rats up to 3,000 mg/kg. The compound has been administered to rats in dosages up to 1,000 mg/kg/day for 5 days with no adverse effects.
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