Microbicide development gets a corporate boost
(Editor’s note: This article discusses products not yet approved by the Food and Drug Administration.)
The long road toward a woman-controlled form of prevention against HIV infection may have just gotten a little shorter with the recent agreement by two major drug companies to license promising compounds at no charge for microbicide development to a nonprofit group.
Bristol-Myers Squibb Co. (BMS) of New York City and Merck & Co. of Whitehouse Station, NJ, have granted the Silver Spring, MD-based International Partnership for Microbicides (IPM) a royalty-free license to develop, manufacture, and distribute specific compounds for use as microbicides in resource-poor countries. The compounds, which are designed to prevent HIV from efficiently entering host cells, are part of a new class of antiretrovirals known as entry inhibitors. The move marks the first time any pharmaceutical company has licensed an anti-HIV compound for development as a microbicide when the class of drugs is so early in development.
The new compounds appear promising. Experiments in female monkeys have for the first time shown that the compounds can protect against an HIV-like virus.1 The candidates analyzed in the current research were first- or second-generation compounds. Newer, more potent versions are now available and will be the ones most likely to move forward in clinical trials, says Ronald Veazey, DVM, PhD, chair of the division of comparative pathology at the Tulane National Primate Research Center in Covington, LA, and lead author of the research paper.
Microbicides may be the best bet in aiding women in the fight against HIV. In 2004, 20 million women around the world were living with HIV, and the upward climb of infections continues, say public health officials.2 If the spread of disease is left unchecked, women soon will make up the majority of the global total of people infected with HIV, they add.2
The new study, funded largely by the National Institute of Allergy and Infectious Diseases, represents the first successful testing of combination microbicides in a primate model. To conduct the research, scientists worked with simian-human immunodeficiency virus (SHIV), a hybrid virus developed from HIV and SIV, which infects only monkeys. Researchers analyzed gels containing two molecules and a peptide in various formulations, all designed to block SHIV from fusing with its target cells at or near the tissue lining of the vagina. Monkeys were given shots of depot medroxyprogesterone acetate (DMPA, Depo-Provera; Pfizer, New York City) to synchronize their menstrual cycles and thin the vaginal membrane to increase their susceptibility to virus infection. Gel was applied vaginally prior to exposing the monkeys to SHIV.
The three inhibitors (BMS-378806 from Bristol-Myers Squibb, CMPD167 from Merck & Co., and C52L, a peptide from Weill Medical College of Cornell University in Ithaca, NY) were effective when used alone and also when tested in combination, research data indicate. Monkeys given the triple combination of microbicides remained virus-free. None of the monkeys experienced vaginal irritation or inflammation from the experimental gels, scientists report.1 Researchers found that the Merck and BMS compounds could be applied up to six hours prior to exposure to the virus and still offer protection, a finding that could be useful if the compounds make it to real-world application.
The International Partnership for Microbicides now is taking the compounds toward the next step in the development pipeline, says Zeda Rosenberg, ScD, chief executive officer of the organization.
Collaboration is an essential part of IPM’s strategy in producing potential microbicide candidates. In March 2004, the organization signed an agreement with a Johnson & Johnson subsidiary, Tibotec Pharmaceuticals of Mechelen, Belgium, to develop the subsidiary’s TMC120 compound as a microbicide.
For some of the compounds, it could be six months to nine months away from the clinic for Phase I safety testing," notes Rosenberg. "We will only know that once we see how compatible the active drugs are in certain formulations," she adds. "We are getting these drugs as active ingredients, and we need now to formulate them for topical use, either in gels or intravaginal rings."
References
- Veazey RS, Klasse PJ, Schader SM, et al. Protection of macaques from vaginal SHIV challenge by vaginally delivered inhibitors of virus-cell fusion. Nature 2005 Oct 30; [Epub ahead of print].
- National Women’s Health Information Center. AIDS Worldwide. Accessed at: www.4woman.gov/hiv/world.cfm.
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