PRO 2000, Under Development by Indevus, Shown to Inhibit HIV and Herpes Simplex Virus Infection Following Human Administration

LEXINGTON, Mass. -- Findings presented at the 12th Conference on Retroviruses and Opportunistic Infections demonstrated that PRO 2000, a candidate topical microbicide under development by Indevus Pharmaceuticals, Inc., retains activity against the human immunodeficiency virus (HIV) and the herpes simplex virus (HSV) following intravaginal administration to HIV-infected women. These data were presented by Marla Keller, MD, assistant professor of medicine at the Mount Sinai School of Medicine, from a study funded by the National Institutes of Health (NIH) that marks the first time that the anti-viral activity of a microbicide has been demonstrated following human application. Microbicides are a class of products being developed to prevent sexually transmitted infections (STIs) when applied topically.

The Mount Sinai researchers conducted the prospective, randomized, double blind, placebo-controlled study among 20 HIV-infected women to assess the antiviral activity of PRO 2000 in cervicovaginal lavage (CVL) fluid collected before and one hour after administration of a single intravaginal dose of PRO 2000 gel or a matched placebo gel. CVL specimens were tested for their ability to prevent HIV and HSV infection of susceptible human cells in culture. Levels of inflammatory cytokines were also measured as markers of acute inflammation.

Analyses showed that CVL obtained after the application of PRO 2000 gel reduced both HIV and HSV infectivity by at least 1000-fold compared to CVL obtained at baseline. The effects were highly statistically significant (p<0.001). In contrast, CVL collected from placebo gel recipients showed little or no anti-viral effect. Furthermore, the researchers found similar low levels of inflammatory cytokines in CVL collected from the drug and placebo groups, indicating that PRO 2000 application did not induce an acute inflammatory response.

"To our knowledge, this is the first time a candidate topical microbicide has been shown to exhibit potent antiviral activity following human administration," said Dr. Keller. "The results indicate that PRO 2000 is sufficiently bioavailable and retains substantial anti-viral activity one hour after application of a single intravaginal dose. The retention of activity against both viruses is particularly significant in that HSV infection may increase the likelihood of HIV infection."

The effectiveness of PRO 2000 in preventing HIV and other sexually transmitted infections among at-risk women is to be assessed in two large clinical trials. A recently initiated NIH-sponsored study will enroll approximately 3,200 women at nine sites in Africa and the United States. In addition, a phase III clinical trial funded by the U.K. Department for International Development is due to start in 2005 and to include approximately 12,000 women in a number of African countries.

The Mount Sinai microbicide research team noted an urgent need for the development of safe and effective vaginal microbicides. While condoms offer protection against STIs, their effectiveness is limited because they require partner initiation or consent. According to the United Nations' 2004 report on the global AIDS epidemic, an estimated 40 million people worldwide are living with HIV, and women account for nearly half of those infected. As stated by the World Health Organization, unprotected sex is the predominant mode of HIV transmission, and genital herpes plays a major role in the sexual spread of HIV.

Source: Indevus Pharmaceuticals, Inc.