PROMISING NEW FLU DRUG UNDER DEVELOPMENT HAS ANTIVIRAL ACTIVITY AGAINST BOTH TYPES OF INFLUENZA IN HUMAN CHALLENGE MODELS
Norbert Brunhuber
Medical Action Communications
908-956-0522
norbert.brunhuber@mac-usa.com
Once-daily, oral RWJ-270201 demonstrated antiviral activity against both types of influenza viruses in human challenge models. These results support the value of conducting additional clinical trials with this agent in humans infected with wild-type influenza virus.
At the annual Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) held September 17–20, 2000, in Toronto, Canada, Dr. Frederick Hayden presented data showing that RWJ-270201 exerted antiviral activity in adult volunteers who were experimentally infected with a strain of either influenza A or influenza B virus. These studies were performed at the University of Virginia in Charlottesville and at the University of Rochester in New York, with funding from the R.W. Johnson Pharmaceutical Research Institute.
RWJ-270201 is a neuraminidase inhibitor (NAI), a new class of anti-influenza drugs that target the viral neuraminidase, an enzyme which is important in viral replication. Previous studies have shown that RWJ-270201 is potent against influenza A and B both in vitro and in a mouse model of influenza.
Two randomized, double-blind, placebo-controlled studies were conducted to evaluate the antiviral activity of RWJ-270201 in healthy adult volunteers experimentally infected with a type A strain (A/Texas/36/91) or a type B strain (B/Yamagata/16/88) of influenza. In each study, the subjects were randomly assigned to receive either placebo or RWJ-270201 for 5 days, beginning 24 hours after viral inoculation. The primary endpoint of these studies was the reduction in viral titers.
In the influenza A study, RWJ-270201 doses ranging from 100 to 400 mg/d had an antiviral effect, and 400 mg administered once daily resulted in a highly significant reduction in the log AUC viral titers (73%) in comparison to placebo. In the influenza B study, subjects receiving RWJ-270201 showed a reduction in the log AUC viral titers compared with placebo at both doses studied (61% reduction for 800mg; 49% for the 800mg loading dose followed by 400mg). RWJ-270201 was well tolerated, and the incidence of adverse events was similar in the treated and control groups of both studies.
In conclusion, oral RWJ-270201, dosed once daily, demonstrated antiviral activity in the treatment of experimental human influenza A and B infections. These results support the conduct of further trials of this agent in wild-type influenza infections in humans. Currently, RWJ-270201 is being tested in Phase III clinical trials.