Adamas Pharmaceuticals, Inc., a privately held company, announced today that a multi-center in vitro study of its proprietary triple combination antiviral drug (TCAD) therapy showed substantially greater potency against seasonal and novel H1N1 influenza viruses than currently recommended single or double therapy and that the triple combination is active against drug-resistant flu strains. The study was presented during an oral presentation at the 49th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC).
Adamas' TCAD therapy consists of a proprietary fixed-dose combination drug product (amantadine and ribavirin), to be administered adjunctively with a neuraminidase inhibitor such as Tamiflu (oseltamivir phosphate, Roche). In this study, using a scientifically accepted in vitro infection model, researchers compared amantadine, ribavirin, and oseltamivir alone and in combination against influenza A viruses that are resistant to either oseltamivir or amantadine, including novel A/H1N1. The results are the product of scientific collaborations with the United States Naval Health Research Center, San Diego; University of Alabama, Birmingham; Utah State University, Logan, Utah; and the Amsterdam Medical Center in the Netherlands.
"These data suggest that the triple combination of amantadine, ribavirin, and oseltamivir was highly synergistic in its ability to inhibit influenza virus replication, including the current circulating novel H1N1 virus. The triple combination approach, because it strikes multiple targets within the viruses, might also help to prevent the development of new resistance in susceptible flu strains," said study investigator Mark Prichard, Ph.D., Professor in the Department of Pediatrics, University of Alabama at Birmingham. "This triple combination approach may represent a highly active antiviral therapy for serious influenza infections, with the potential to address the current limitations of antiviral potency and drug resistance."
The study results showed that the triple combination was highly synergistic in vitro, and the synergy of TCAD therapy was significantly greater than the synergy of double combinations against both susceptible and resistant viruses. Importantly, the study revealed that oseltamivir and amantadine in the triple combination contributed to antiviral activity against oseltamivir-resistant and amantadine-resistant viruses, respectively, at concentrations where they had no activity as single agents, and at concentrations that are clinically relevant.