Therapeutic Focus - HIV
About HIV
HIV/AIDS is a chronic and growing problem of global significance. According to the Centers for Disease Control and Prevention (CDC), over one million persons in the United States are currently living with HIV/AIDS, with an estimated 40,000 persons in the U.S. becoming infected with HIV each year.
If the HIV/AIDS epidemic in the U.S. and other developed countries is sobering, the problem is dramatically expanded on a global scale, especially in developing nations where education, sanitation and medical care are inadequate. In a recent report, UNAIDS/WHO (AIDS Epidemic Update, Dec. 2005) document a staggering international problem:
- There are over 40 million people currently infected by HIV, of which 38 million are men, 17.5 million are women, and 2.3 million are children;
- Approximately 5 million people were newly infected with HIV in 2005, over 4 million of which were adults, the remainder were children;
- More than 3 million people died of AIDS in 2005; and
- Between 1 in 5 to 1 in 3 pregnant women in some Sub-Saharan African nations are infected with HIV.
While dramatic improvements in education and coordinated prevention of HIV transmission will need to take place to slow down and halt the spread of the virus, there remains an urgent need for new, safe and effective modalities for HIV/AIDS disease management.
While more than 20 HIV/AIDS vaccines are currently under study, the complexities of viral biology, the logistics of clinical trial conduct, intellectual property issues, and development and regulatory costs suggest that an effective vaccine(s) won’t be readily available. As a result, much research effort has been spent on development of antiviral drugs and microbicides. Microbicides are a prevention tool women can control and could have a substantial impact on the epidemic. Currently, there are more than one dozen HIV microbicides in clinical research, including soaps, acid buffering agents, seaweed derivatives and anti-HIV compounds. Modeling indicates that even a 60%-efficacious microbicide could have considerable impact on HIV spread. If used regularly by just 20% of women in countries with substantial epidemics, hundreds of thousands of new infections could be averted every year.
Several drugs are approved in the U.S. for the treatment of HIV, and belong to 4 classes depending on their general mode of action:
- Protease inhibitors, disable the HIV-specific protease the virus needs for making copies of itself. There are 9 approved products in this class;
- Nucleoside reverse transcriptase inhibitors (NRTIs), which are faulty versions of genetic building blocks the virus needs to reproduce. There are 12 approved products in this class, including drug combinations;
- Non-nucleoside reverse transcription inhibitors (NNRTIs), which bind to and disable reverse transcriptase, an enzyme HIV needs to make copies of itself. There are 3 approved products in this class; and
- Fusion inhibitors, which work by blocking HIV entry into cells. There is only one approved product in this class, Roche/Trimeris’ Fuzeon® (T-20; Enfuvirtide).
While these drugs, used singly or in combination "cocktails" have helped retard viral spread and development of AIDS, their high cost, poor availability in the developing world, and, for some classes, a high susceptibility to HIV resistance, continue to drive the need for better drugs whose mode of action can overcome these challenges.
Intrucept Biomedicine’s approach is to develop drugs that prevent HIV from entering its target cells and thus prevent the chronic establishment of the pathogen. Intrucept’s lead HIV compound belongs to the fusion inhibitor, or entry inhibitor, class of drugs, of which there is currently only one approved member (Enfuvirtide). Because Enfuvirtide blocks HIV/cell-receptor interaction at a small molecular target site, viral mutations in this region are already leading to strains of HIV that are Enfuvirtide-resistant. Resistance, coupled with high cost and multiple daily dosing required with Enfuvirtide, create an opportunity for Intrucept’s new fusion inhibitor drug to satisfy an unmet need in this category.
