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Experimental influenza therapy shows activity against resistant strains, H1N1
A fixed-dose combination of amantadine and ribavirin administered adjunctively with a neuraminidase inhibitor such as oseltamivir may be the future for treating drug resistant and pandemic influenza strains.
Data from a multicenter in vitro trial indicated that a triple combination antiviral drug (TCAD) therapy had greater potency against seasonal and novel influenza A H1N1 strains compared with currently recommended therapies.
“This triple combination may represent a highly active anti-flu therapy for influenza A infection, with the potential to address the current limitations of antiviral potency and widespread drug resistance,” Mark Prichard, PhD, professor in the department of pediatrics at the University of Alabama, Birmingham, said at the American Academy of Microbiology’s 49th Interscience Conference on Antimicrobials and Chemotherapy.
Prichard and colleagues from several sites in the United States and Europe compared the effect of each drug alone and then in combination against seasonal influenza A viruses, including novel H1N1, and found that TCAD had five-to-20 fold greater activity against influenza compared with any single drug alone and was more synergistic than any double combination.
Data also indicated that when oseltamivir and amantadine were incorporated into TCAD, they showed activity against oseltamivir- and amantadine-resistant influenza strains.
This triple combination approach may also help prevent the development of resistant influenza strains in the future because it works against multiple targets within the virus, according to Prichard.
The researchers believe that this interaction may result in a tighter constraint of viral replication and may increase the genetic barrier to resistance.
“Nearly every single circulating influenza virus strain is resistant to either the adamantines or the neurominidase inhibitors, and since these represent the only two approved classes of drugs we find ourselves in a bit of a pickle,” Amy Patick, PhD, vice president of research at Adamas Pharmaceutical’s, the company developing the therapy, said during a press conference. “The current antiviral drugs when given alone as monotherapy, which is the standard of care, lack the overall potency and are not able to effectively stop resistant viruses from replicating.”
In response to this need, Patick announced Adamas’ plans for upcoming clinical trials to explore TCAD’s efficacy compared with oseltamivir monotherapy. She said that the company has begun enrolling patients for a 40-site, 250-patient trial in the southern hemisphere that will explore TCAD’s effect in immunocompromised patients. A second Northern hemisphere trial is planned for immunocompetent patients. – by Nicole Blazek