Innovative Flu Antiviral Shows Positive Phase 1 Study Results

Antiviral AL-794 is a novel inhibitor of the endonuclease function of the influenza virus polymerase complex

cold man in hat and coat

Last flu season was another annual reminder of how the influenza vaccine effectiveness can vary each year.

During the 2017/18 flu season, the overall adjusted vaccine effectiveness (VE) against influenza A and influenza B virus infection was reported by the Centers for Disease Control and Prevention (CDC) to be just 36 percent.

Fortunately, the current information suggests that the available class of antiviral agents, the neuraminidase-inhibitors (NAIs), work well against the influenza viruses.

The best known NAIs are oseltamivir (Tamiflu), zanamivir ( Relenza), and peramivir (Rapivab). 

But resistance to these antiviral drugs remains a constant threat, as evidenced by the rapid emergence of NAI resistance in influenza A(H1N1) viruses in 2008. 

Thus, there appears to be an urgent need for the development of additional antiviral agents with differing mechanisms of action that could be used in the case of NAI resistance.

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In the current issue of The Journal of Infectious Diseases, researchers reported on the effects of AL-794, a novel inhibitor of the endonuclease function of the influenza virus polymerase complex, which they evaluated in the human challenge model.

In this phase 1 clinical study, subjects were inoculated with influenza A/Perth/16/2009 (H3N2), and administration of AL-794 at the onset of viral shedding was associated with dose- and concentration-related decreases in the amount of subsequent virus shedding and reductions in influenza-related clinical symptoms.

This experimental drug was well tolerated, and no drug-resistant viruses were recovered in this small sample set.

Based upon these encouraging study results, the investigators plan to move forward with further clinical development.

The authors of study certified no potential conflicts of interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.