In Vitro Study of Adamas Pharmaceuticals' Triple Combination Antiviral Drug Therapy Shows Activity Against Drug-Resistant Influenza Viruses
Data Presented At 2009 Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC)
SAN FRANCISCO, Sept. 13 /PRNewswire/ -- 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.
According to the study investigators, virtually all clinical isolates of seasonal influenza in 2009 have been found to be resistant to either the adamantanes or oseltamivir. They caution that the development of resistance to currently recommended therapies may undermine their utility. While currently limited in scope, the first cases of multi-drug resistant novel influenza A/H1N1 flu are also now being reported and will need to be addressed.(1)
"Drug resistant seasonal influenza and emerging cases of multi-drug resistant novel influenza A/H1N1 virus are creating an immediate need for alternative strategies to currently available antiviral therapies," said Gregory Went, Ph.D., Chief Executive Officer and Chairman of Adamas. "The impact to the healthcare system as a result of increased admissions for those with serious flu is exacerbated during a pandemic so we believe our work is very timely. "
The CDC and WHO recommend the use of antiviral drugs for treating serious cases of influenza infection(2). Antiviral drugs that are both potent and effective against drug-resistant strains also may be important for limiting transmission of the swine flu virus during the pandemic.(3)
The data were presented on September 13, 2009 at 10:45 am. ICAAC will also feature the Adamas study at a press conference at 8:30 a.m. Monday, September 14, 2009. Reporters unable to attend the meeting or press conference can watch it live at http://www.ustream.tv/channel/49th-icaac.
Adamas is pioneering triple-combination antiviral drug (TCAD) therapy for influenza, which is designed to inhibit viral replication at multiple points during the virus life cycle. 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, acts synergistically to provide a much higher level of antiviral activity than single or double drug combinations. 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. Adamas is accelerating development of its TCAD therapy for influenza A by conducting a Phase 2 clinical trial in the Southern Hemisphere where the novel influenza A/H1N1 pandemic is active, and is preparing to initiate a clinical study of TCAD therapy for influenza A in North America during this upcoming flu season.
Adamas is an emerging pharmaceutical company focused on developing small molecule, Advantaged Therapeutics(TM) 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.
(3) Initial human transmission dynamics of the pandemic (H1N1) 2009 virus in North America. Influenza and Other Respiratory Viruses; Volume 3, Issue 5, Date: September 2009, Pages: 215-222
Babak Pourbohloul, Armando Ahued, Bahman Davoudi, Rafael Meza, Lauren A. Meyers, Danuta M. Skowronski, Ignacio Villasenor, Fernando Galvan, Patricia Cravioto, David J. D. Earn, Jonathan Dushoff, David Fisman, W. John Edmunds, Nathaniel Hupert, Samuel V. Scarpino, Jesus Trujillo, Miguel Lutzow, Jorge Morales, Ada Contreras, Carolina Chavez, David M. Patrick, Robert C. Brunham
SOURCE Adamas Pharmaceuticals, Inc.
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