Vivecon™ (MPC-9055)
Vivecon is a novel, potent, small-molecule drug candidate designed by Myriad Pharmaceuticals for the oral treatment of human immunodeficiency virus 1 (HIV-1) infection. Vivecon is currently in Phase 1 clinical development.
About Vivecon (MPC-9055)
Vivecon is a potent small-molecule maturation inhibitor being developed for the oral treatment of HIV infection. Vivecon targets a unique cleavage event in the HIV life cycle, inhibiting the processing of a Capsid-Spacer 1 intermediate of the Gag protein. This results in a noninfectious virion, and prevents subsequent rounds of HIV infection. Vivecon does not inhibit HIV protease. As a viral maturation inhibitor, Vivecon has the potential to be the first drug in a new class of agents for the treatment of HIV-1 infection.
Vivecon has been tested extensively in preclinical in vitro and in vivo studies to establish antiviral activity and assess safety. It demonstrated potent antiviral activity, with an average HIV IC 50 value of 10 nanomolar and an approximate 1,000-fold in vitro therapeutic index. Vivecon was also shown to be active against viral strains that are resistant to the currently marketed anti-HIV drugs, including nucleoside reverse transcriptase inhibitors such as AZT™, non-nucleoside reverse transcriptase inhibitors such as Efavirenz™, and protease inhibitors such as Ritonavir™. Vivecon has been well-tolerated and exhibits a favorable safety profile in a variety of preclinical studies.
Myriad's anti-viral drug discovery program began with the discovery of the interaction between the HIV Gag protein and the human host protein, TSG101, in the viral budding/maturation pathway of HIV. This research was first published on October 5, 2001 [1], and expanded upon in September, 2003 [2]. Both articles were featured as the cover article in the journal Cell. Myriad scientists have made subsequent discoveries regarding the biology of HIV viral particle maturation, viral fusion with host cells and intra-cellular events in the life cycle of HIV which has enabled Myriad to identify additional novel targets which may inhibit HIV infection.
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About HIV and AIDS
According to the U.S. Centers for Disease Control and Prevention (CDC), there are approximately 1.1 million persons in the United States living with HIV/AIDS. In 2005, the estimated number of new diagnoses of AIDS in the United States and dependent areas was 41,897 per year. The estimated number of deaths in 2005 of persons with AIDS in the United States and dependent areas was 17,011.
According to the United Nations UNAIDS program, over 33 million people throughout the world are living with HIV/AIDS, and as of January 2006, UNAIDS and the World Health Organization (WHO) estimate that AIDS has killed more than 25 million people since it was first recognized on June 5 , 1981, making it one of the most destructive epidemics in recorded history. Some 2.5 million people were newly infected with the virus in 2007, or 6,800 new infections every day.
Standard antiviral therapies for the treatment of HIV/AIDS, while effective for varying lengths of time, can be rendered inadequate for viral suppression by the emergence of drug-resistant virus, which can include resistance to entire mechanistic classes of drugs. An increase in resistance to antiviral therapy has been observed with increasing length of time that antiviral agents have been in use. Thus, there exists a significant unmet medical need for a highly potent antiviral agent with a novel mechanism, to provide additional antiviral treatment and improve on the limitations of current therapies. Vivecon may provide a novel treatment option in HIV/AIDS patients who experience a suboptimal response to standard anti-HIV therapies.
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Clinical Trial
The current clinical development plan for Vivecon is designed to expedite the drug candidate through the clinical development path. The first Phase 1 trial is formatted as a single ascending dose in healthy volunteers and is designed to assess the safety, tolerability, and pharmacokinetics of the compound.
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References
- Garrus J.E., et al, Tsg101 and the Vacuolar Protein Sorting Pathway Are Essential for HIV-1 Budding. Cell 2001 107 : 55-65. PMID:
11595185
- von Schwedler , U.K. , et al, The Protein Network of HIV Budding. Cell 2003 114 : 701-713. PMID:
14505570
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