BioCryst Broad-Spectrum Antiviral BCX4430 Highly Effective Against Yellow Fever In A Preclinical Disease Model
BioCryst Pharmaceuticals, Inc. (NASDAQ:BCRX) today announced proof-of-principle data demonstrating that BCX4430 is efficacious and well tolerated in a preclinical disease model for evaluating efficacy against yellow fever virus infection. BCX4430 is the lead compound in BioCryst’s broad-spectrum antiviral (BSAV) research program. The objective of BioCryst’s BSAV program is to develop broad-spectrum parenteral and oral therapeutics for viruses that pose a threat to national health and security.
A presentation entitled “BCX4430, an adenosine analog, with potent activity against yellow fever virus in a hamster model,” will be presented by Dr. Justin Julander at the 2nd Antivirals Congress in Cambridge, MA today at 5:10PM E.T.
These studies comprehensively evaluated the efficacious dose, dose duration, and therapeutic use of parenteral BCX4430 in the treatment of yellow fever infection. Syrian Golden Hamsters–a widely accepted model for establishing efficacy against yellow fever —virus were inoculated intraperitoneally with ten times the cell culture infectious dose (CCID 50) of yellow fever virus (Jimenez strain) and treated parenterally with BCX4430 administered either once or twice daily for 4 to 7 days. In studies with treatment just prior to infection or delayed up to 4 days after infection, BCX4430 treated animals had significantly (p<0.001) improved survival (80–100%) compared to animals receiving saline placebo (20-30%). It is important to note that in this model, serum viral titers peak at day four after infection, indicating that BCX4430 has the potential to be an effective therapeutic when administered as pre-exposure prophylaxis; as post-exposure prophylaxis during the virus incubation period; and as a treatment during the prodromal period and symptomatic disease. Treated animals also exhibited significantly lower viral titers in serum, improved weight gain, and decreased liver damage as measured by lower levels of alanine transaminase and aspartate transaminase.
In addition, BCX4430 demonstrated a wide therapeutic index of 50 with a minimum effective dose of 4 mg/kg/day (p<0.05 vs control), as measured by survival, and a maximum tolerated dose of 200 mg/kg/day, as measured by percent weight change.
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