EMERYVILLE, Calif., March 15 /PRNewswire/ -- Adamas Pharmaceuticals, Inc., a privately held company, announced today results from in vivo animal studies and in vitro tests demonstrating that its triple combination antiviral drug (TCAD) therapy is superior relative to double combinations and monotherapy against multiple strains of pandemic and avian influenza viruses. Results of these studies were presented Sunday evening in an oral session at the XII International Symposium on Respiratory Viral Infections being held in Taipei.
Currently, virtually all influenza A viruses are resistant to at least one approved antiviral and mounting evidence suggests that monotherapy leads to single and multi-drug resistance, creating a pressing need for new influenza therapies.
Data presented by Adamas at the conference demonstrates that the triple combination of amantadine, ribavirin, and oseltamivir is highly active against susceptible and resistant influenza A virus infection in mouse models. In addition, the triple combination was shown to suppress the generation of resistant influenza A viruses in vitro. These data confirm findings from recently published in vitro studies (PLoS One, AAC), and answer fundamental questions about the viral kinetics of susceptible and resistant strains of the influenza A virus in response to TCAD.
"With these data, Adamas and its collaborators continue to build a strong case for triple combination therapy in influenza," said Richard J. Whitley, M.D., Professor of Pediatrics, Microbiology and Medicine at the University of Alabama at Birmingham. "They have demonstrated that the addition of a third drug is critical to increase the genetic barrier to resistance for influenza. Importantly, the use of a triple drug combination also results in a substantial increase in efficacy over double combinations at clinically relevant concentrations, allowing the continued use of drugs to which the virus has evolved resistance. If validated in human studies, TCAD could fill a significant gap in the treatment of influenza."
About the in vivo and in vitro Studies
At the meeting yesterday, Dr. Jack Nguyen of Adamas presented data from in vivo studies demonstrating that TCAD is highly efficacious against susceptible H5N1 and resistant pandemic 2009 H1N1 in mouse treatment models in which physiologic concentrations of oseltamivir provided little or no protection. These data confirmed the increase in potency of TCAD observed in vitro, showing that TCAD is significantly more efficacious than double combinations, resulting in greater than 90% survival in the treated mice. Moreover, amantadine contributed to the efficacy of TCAD against amantadine-resistant pandemic 2009 H1N1 virus.
In additional in vitro experiments, influenza virus was replicated in the presence of clinically relevant concentrations of single agents, double combinations and TCAD therapy over a 15 day time period. Treatment with the single agents and double combination resulted in the complete breakthrough of resistant viruses, while triple therapy effectively impeded the development of resistance.
The Need for Broad Spectrum Antiviral Therapy
According to the World Health Organization, more than 17,000 deaths occurred in the U.S. alone this flu season due to the pandemic novel H1N1 virus, highlighting the need for an effective broad spectrum antiviral therapy, especially for patients severely ill with influenza for whom current antivirals are ineffective. The greatest impact of influenza infection is felt in at-risk groups especially vulnerable to infections such as patients with cardiovascular disease, diabetes, asthma and those who are immunocompromised. These individuals are at a higher risk of hospitalization and ICU admission, as well as other complications related to influenza. Resistance to at least one class of antiviral drugs in all circulating strains complicates the diagnosis and treatment of flu.
"Through our comprehensive preclinical program, we have demonstrated the broad spectrum effect of TCAD therapy with the potential to overcome baseline resistance while imposing a high genetic barrier to impede the generation of resistant influenza virus strains," said Gregory T. Went, PhD., CEO and Chairman of Adamas Pharmaceuticals. "This accomplishment is a critical foundation for our clinical program and our long-term commitment to providing a solution that meets the needs of physicians in treating patients with influenza infection."
About TCAD Therapy
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 independent mechanisms of action, act synergistically to provide a much higher level of antiviral activity than single or double drug combination therapies. In preclinical studies to date, TCAD therapy also has been found to provide greater antiviral activity across more than 13 strains of seasonal, pandemic, and avian influenza A (H1N1, H3N2 and H5N1) virus, including six amantadine resistant strains and two oseltamivir-resistant strains. TCAD therapy for influenza A is currently being investigated in a Phase 2 human clinical study.
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 product development is to identify unmet needs where existing drugs 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.
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