Efficacy and Safety of the Neuraminidase Inhibitor Zanamivir in the Treatment of Influenzavirus Infections
Frederick G. Hayden, M.D., Albert D.M.E. Osterhaus, D.V.M., Ph.D., John J. Treanor, M.D., Douglas M. Fleming, F.R.C.G.P., Ph.D., Fred Y. Aoki, M.D., Karl G. Nicholson, M.D., Arthur M. Bohnen, M.D., Hilary M. Hirst, Oliver Keene, M.A., M.S., Kevin Wightman, B.S., for The GG167 Influenza Study Group
Background The sialic acid analogue zanamivir (GG167) is a selectiveinhibitor of influenza A and B virus neuraminidases. These viralenzymes are essential for the release of virus from infectedcells, and they may also reduce the inactivation of virus byrespiratory secretions. When administered experimentally directlyto the respiratory tract, zanamivir has potent antiviral effects.We assessed the therapeutic activity of zanamivir in adultswith acute influenza.
Methods We conducted separate randomized, double-blind studiesin 38 centers in North America and 32 centers in Europe duringthe influenza season of 1994–1995. A total of 417 adultswith influenza-like illness of <48 hours' duration were randomlyassigned to one of three treatments: 6.4 mg of zanamivir byintranasal spray plus 10 mg by inhalation, 10 mg of zanamivirby inhalation plus placebo spray, or placebo by both routes.Treatments were self-administered twice daily for five days.
Results Of 262 patients with confirmed influenzavirus infection(63 percent of all patients), the median length of time to thealleviation of all major symptoms was one day shorter (fourdays vs. five days) in the 88 patients given inhaled and intranasalzanamivir (P=0.02) and the 85 patients given inhaled zanamiviralone (P=0.05) than in the 89 patients given placebo. Amongthe infected patients who were febrile at enrollment and amongthose who began treatment within 30 hours after the onset ofsymptoms, the median time to the alleviation of major symptomswas four days in both zanamivir groups and seven days in theplacebo group (P<0.01). Viral titers of nasal washings inthe group given inhaled and intranasal zanamivir were significantlylower than those in the placebo group. The topically administeredzanamivir was well tolerated.
Conclusions In adults with influenza A or B virus infections,direct administration of a selective neuraminidase inhibitor,zanamivir, to the respiratory tract is safe and reduces symptomsif begun early.
Source Information
From the University of Virginia, Charlottesville (F.G.H.); Erasmus University, Rotterdam, the Netherlands (A.D.M.E.O., A.M.B.); University of Rochester, Rochester, N.Y. (J.J.T.); the Northfield Health Centre, Birmingham, United Kingdom (D.M.F.); University of Manitoba, Winnipeg, Canada (F.Y.A.); University of Leicester, Leicester, United Kingdom (K.G.N.); Glaxo Wellcome, Research Triangle Park, N.C. (H.M.H.); and Glaxo Wellcome, Greenford, United Kingdom (O.K., K.W.).
Address reprint requests to Dr. Hayden at Box 473, University of Virginia Health Sciences Center, Charlottesville, VA 22908.
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