EMERYVILLE, Calif., Feb. 22 /PRNewswire/ -- Adamas Pharmaceuticals, Inc., a privately held company, reported today on the publication of results from a preclinical study that demonstrated the synergistic effects of triple combination antiviral drug (TCAD) therapy against multiple strains of seasonal, pandemic, and avian influenza A (H1N1, H3N2 and H5N1) virus, including three strains of amantadine resistant pandemic H1N1 and two strains of oseltamivir resistant seasonal H1N1.
The results of this study have been published in PLoS One under the title: Triple Combination of Amantadine, Ribavirin, and Oseltamivir is Highly Active and Synergistic Against Drug Resistant Influenza Virus Strains In Vitro. PLoS One is an interactive open-access journal for the communication of all peer-reviewed scientific and medical research published by the Public Library of Science (PLoS). Interested parties may view the article on the PLoS website under Presentations and Publications.
The data demonstrated that amantadine, ribavirin and oseltamivir, when administered as components of a triple combination therapy, had a synergistic effect (i.e. enhanced antiviral activity) against multiple amantadine- and oseltamivir-resistant virus strains. The data also demonstrated that the antiviral activity of the TCAD regimen is greater than the antiviral activity of any double combination. Further, when investigating amantadine-resistant virus strains against which amantadine had no significant antiviral activity as a single agent, the addition of amantadine at clinically relevant concentrations to the combination of ribavirin and oseltamivir resulted in a dose dependent inhibition of virus replication. This was similarly observed for oseltamivir in strains that were oseltamivir resistant. These data demonstrate that the TCAD therapy may have broad-spectrum activity against the circulating resistant influenza A strains, including novel influenza A/H1N1, the pandemic influenza strain.
"Given the fact that the majority of influenza A viruses are resistant to at least one antiviral, these data suggest the advantage of a triple combination drug therapy approach over double combinations or monotherapy," said Gregory Went, Ph.D., chief executive officer and chairman of Adamas. "We are encouraged about the potency of TCAD therapy measured in preclinical studies and look forward to continued validation of TCAD therapy with our academic and clinical partners."
About TCAD
Adamas is pioneering triple combination antiviral drug (TCAD) therapy for influenza, which is designed to inhibit viral replication at multiple points in the virus proliferation pathway. TCAD therapy includes Adamas' investigational proprietary fixed-dose combination of amantadine and ribavirin, to be administered adjunctively with a neuraminidase inhibitor such as Tamiflu ® (oseltamivir phosphate, Roche). Preclinical data indicate that the in vitro combination of these drugs, each with their own mechanism of action, act synergistically to provide a much higher level of antiviral activity than single or double drug combination therapies. In in vitro studies to date, TCAD therapy also has been found to provide greater antiviral activity across multiple strains of influenza, even those resistant to single pharmaceutical agents. TCAD therapy for influenza A is currently being investigated in a Phase 2 human clinical study.
About Adamas
Adamas is an emerging pharmaceutical company focused on developing small molecule Advantaged Therapeutics to treat neurological and infectious diseases, including influenza A, the cause of the current flu pandemic. Adamas' approach to pharmaceutical development is to identify synergistic drug mechanisms that can be developed as optimized combination drug therapies to increase safety, efficacy and compliance, thus improving upon the standard of care. Adamas is headquartered in Emeryville, California, with operations in Bangalore, India. For more information about Adamas, please visit www.adamaspharma.com.
SOURCE Adamas Pharmaceuticals, Inc.
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The results of this study have been published in PLoS One under the title: Triple Combination of Amantadine, Ribavirin, and Oseltamivir is Highly Active and Synergistic Against Drug Resistant Influenza Virus Strains In Vitro. PLoS One is an interactive open-access journal for the communication of all peer-reviewed scientific and medical research published by the Public Library of Science (PLoS). Interested parties may view the article on the PLoS website under Presentations and Publications.
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The data demonstrated that amantadine, ribavirin and oseltamivir, when administered as components of a triple combination therapy, had a synergistic effect (i.e. enhanced antiviral activity) against multiple amantadine- and oseltamivir-resistant virus strains. The data also demonstrated that the antiviral activity of the TCAD regimen is greater than the antiviral activity of any double combination. Further, when investigating amantadine-resistant virus strains against which amantadine had no significant antiviral activity as a single agent, the addition of amantadine at clinically relevant concentrations to the combination of ribavirin and oseltamivir resulted in a dose dependent inhibition of virus replication. This was similarly observed for oseltamivir in strains that were oseltamivir resistant. These data demonstrate that the TCAD therapy may have broad-spectrum activity against the circulating resistant influenza A strains, including novel influenza A/H1N1, the pandemic influenza strain.
"Given the fact that the majority of influenza A viruses are resistant to at least one antiviral, these data suggest the advantage of a triple combination drug therapy approach over double combinations or monotherapy," said Gregory Went, Ph.D., chief executive officer and chairman of Adamas. "We are encouraged about the potency of TCAD therapy measured in preclinical studies and look forward to continued validation of TCAD therapy with our academic and clinical partners."
About TCAD
Adamas is pioneering triple combination antiviral drug (TCAD) therapy for influenza, which is designed to inhibit viral replication at multiple points in the virus proliferation pathway. TCAD therapy includes Adamas' investigational proprietary fixed-dose combination of amantadine and ribavirin, to be administered adjunctively with a neuraminidase inhibitor such as Tamiflu ® (oseltamivir phosphate, Roche). Preclinical data indicate that the in vitro combination of these drugs, each with their own mechanism of action, act synergistically to provide a much higher level of antiviral activity than single or double drug combination therapies. In in vitro studies to date, TCAD therapy also has been found to provide greater antiviral activity across multiple strains of influenza, even those resistant to single pharmaceutical agents. TCAD therapy for influenza A is currently being investigated in a Phase 2 human clinical study.
About Adamas
Adamas is an emerging pharmaceutical company focused on developing small molecule Advantaged Therapeutics to treat neurological and infectious diseases, including influenza A, the cause of the current flu pandemic. Adamas' approach to pharmaceutical development is to identify synergistic drug mechanisms that can be developed as optimized combination drug therapies to increase safety, efficacy and compliance, thus improving upon the standard of care. Adamas is headquartered in Emeryville, California, with operations in Bangalore, India. For more information about Adamas, please visit www.adamaspharma.com.
SOURCE Adamas Pharmaceuticals, Inc.
