August 4, 2008
At today's session, Vaccines and Microbicides: Where Do We Go from Here?, Zeda Rosenberg updated the state of research into microbicides. Her presentation spoke of renewed hope that the current pipeline of experimental drugs could, in a year or two, result in strong candidates for protecting women against HIV infection. This tone was in marked contrast to the general sense of disappointment that has permeated this important field for the past few years.
Microbicides are substances designed to prevent HIV and other sexually transmitted infections (STIs). They come in a variety of products, such as gels, rings, films, tablets and capsules. As a woman-controlled method of contraception and STI prevention, the current candidates are being studied as vaginally applied products. Rectal application studies are being considered, though these are still in their infancy.
Microbicides offer women more control over their health. Other benefits to using these products include a low systemic exposure to the drug since it's not taken by mouth, fewer possible side effects, and less chance for resistance. Although the potential for these products is real, it's clear that one microbicidal strategy will not satisfy all women. Some women may also need or want to use more than one product.
Her presentation started by acknowledging the setbacks over recent years in microbicide research. No less than 10 studies were stopped due to lack of effectiveness and safety issues. However, two studies are still ongoing: BufferGel and PRO 2000.
The bulk of her presentation focused on the next generation of products, many of which are antiretrovirals (ARVs). ARVs are potent and effective drugs used to inhibit and control viruses, including HIV. Many of these candidates have already been developed for other uses, resulting in a good deal of accumulated safety and efficacy information.
Among the candidates furthest along in study is topical tenofovir. Tenofovir is a widely used HIV treatment, sold by itself as Viread and as part of the fixed-dose combination pills, Truvada and Atripla. Eight safety studies have been completed, and the next phase is being planned. Of all the microbicide candidates, this drug has the most advanced research backing its use, especially against HIV.
The highly potent NNRTI, dapirivine, is also being tested. Originally developed as a pill to treat HIV, this drug has been studied in a dozen different studies. Several dosage forms are in development, and a Phase 3 study is planned for 2010. The efficacy studies show a good level of drug release.
Two other NNRTIs are in study: UC781 and PC815. UC781 appears to be highly potent after the completion of four Phase 1 studies. Two more are being planned, as well as two Phase 1 studies examining tolerance in men. PC815 appears to be potent, though prevention studies are ongoing in primates. Phase 1 studies are planned for 2009.
Another HIV drug, the CCR5 antagonist maraviroc, is being studied as a topical gel. It's already well studied in treating HIV, and early assessment of its effectiveness as a microbicide is ongoing.
Aside from these, another nine candidates stand in the pipeline. These include BMS794, m167, RANTES analogs, L755 peptide and pyrimidinediones, among others.
The lessons learned from the failure of the earlier candidates are helping guide research on the newer generation of microbicides. More focus has been placed on products with superior safety profiles along with a plan to advance only the strongest candidates. Additionally, highly potent ARVs show a renewed promise for success. The potential for microbicides with multiple targets is being studied as well. These factors can help restructure the microbicide research agenda and produce new products for women, and later for men, to use.
Project Inform is encouraged by this level of current research and hopes that solid candidates will come forth in the near future. It's clear from a global perspective that these products can mean life or death for millions of women. In the US, the CDC's recent announcement that new infections in the US are 40% higher than previously thought shows the dire need for new prevention efforts domestically. Although these vaginally dosed products are a welcomed addition to HIV prevention, microbicides must also be developed in rectal use, for those who engage in anal sex.
Project Inform continues to support, advocate and provide leadership around biomedical prevention that further reduces the number of new infections, like microbicides. Included in this is our leadership role within the newly formed PrEP (Pre Exposure Prophylaxis) Working Group, founded by CHAMP. As a member of the group, Project Inform's activities will be focused primarily on addressing the financing, delivery and access related issues for PrEP.