Key result
In healthy volunteers experimentally infected with RSV, GS-5806 produced a mean 4.2 log10 reduction in peak viral load and significantly reduced disease severity compared to placebo.
Why the study?
Does GS-5806 reduce viral load and disease severity in healthy human volunteers experimentally infected with RSV?
RCT
Does GS-5806 reduce viral load and disease severity in healthy human volunteers experimentally infected with RSV?
GS-5806 is a potent, once-daily oral RSV fusion inhibitor that significantly reduces viral load and disease severity in a human challenge model.
Answers are grounded in this paper and cite their sources.
Supports progression of GS-5806 to patient trials; extends challenge-model data to oral RSV fusion inhibition.
GS-5806 is a novel, orally bioavailable RSV fusion inhibitor discovered following a lead optimization campaign on a screening hit. The oral absorption properties were optimized by converting to the pyrazolo[1,5-a]-pyrimidine heterocycle, while potency, metabolic, and physicochemical properties were optimized by introducing the para-chloro and aminopyrrolidine groups. A mean EC50 = 0.43 nM was found toward a panel of 75 RSV A and B clinical isolates and dose-dependent antiviral efficacy in the cotton rat model of RSV infection. Oral bioavailability in preclinical species ranged from 46 to 100%, with evidence of efficient penetration into lung tissue. In healthy human volunteers experimentally infected with RSV, a potent antiviral effect was observed with a mean 4.2 log10 reduction in peak viral load and a significant reduction in disease severity compared to placebo. In conclusion, a potent, once daily, oral RSV fusion inhibitor with the potential to treat RSV infection in infants and adults is reported.
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Mackman et al. (2015) conducted an RCT in RSV infection. GS-5806 vs. placebo was evaluated on peak viral load (mean 4.2 log10 reduction). In healthy volunteers experimentally infected with RSV, GS-5806 produced a mean 4.2 log10 reduction in peak viral load and significantly reduced disease severity compared to placebo.
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