On Monday morning, Dr Polly Harrison of the Alliance for Microbicide Development spoke at the Microbicides 2002 meeting in Antwerp on the range of products under active development.
Her group, which includes as members most of the companies working in the field, now carries out regular surveys and maintains a publicly available database (follow the link above to the Alliance website for details) of possible products and where they have got to.
Currently, there are at least 52 different products being actively developed. This is a slightly lower number than at times in the past, reflecting some weeding out of unsuitable compounds. There were also at least two different delivery devices and one special formulation being developed, which might be an area deserving more research.
One product, CarraGuard, is now entering full-scale Phase III trials, with two more in Phase II/III trials, two in Phase II and 9 in Phase I. There might be another 20 with some animal test results available and 18 which have shown some activity in cell cultures and similar systems.
(The meaning of these Phases is a little different in microbicide development than it is in drug or vaccine development, as there is no simple equivalent to achieving therapeutic drug levels or measurable immune responses. Therefore Phase I and Phase II are both likely to be concerned with safety only, with efficacy of any kind left for Phase II/III.)
What was noticeable about the kinds of agents now being looked at was a shift away from more general microbicides, which it is hoped would act against a range of STIs as well as HIV, towards agents which would only work against HIV. In particular, with the failure of nonoxynol-9, a number of related compounds have (sensibly) been dropped for further research. This raises important issues, since the market for HIV-only agents for women would probably be far more limited in wealthier countries than in developing countries, and because women in developing countries also have a great need for protection against STIs other than HIV. These newer agents might therefore need to be combined in practice with more general agents. This would make clinical testing and regulatory approval more complicated than it would be for single agents.
Some approaches had been abandoned, others had evolved into something entirely different. For example, work on cyanovirin – a naturally produced substance that appears to bind specifically to HIV – is now focussed on engineering bacteria such as lactobacilli to produce this, which could live in the vagina and provide enhanced protection for long periods. Similarly, lactobacilli were being engineered to express the CD4 protein in the hope HIV would bind to the bacteria and be unavailable for transmission.
Several presentations were based on a WHO-sponsored meeting on the Scientific basis for regulatory decisions on microbicides, which was evidence of a continuing and very necessary discussion between regulators, advocates and product developers on what conditions need to be met for a product to be licensed around the world.
Posters presented at the meeting described work with a number of these compounds, although obviously no human efficacy results are available yet for any of them. Among the newer agents, a non-nucleoside reverse transcriptase inhibitor called UC-781 being developed by BioSyn in the USA, and an entry/fusion inhibitor called SPL7013 being developed by Star Pharma in Australia, are closest to clinical trials.
There is an overview of microbicides in development on aidsmap.com - follow this link for details. This will be updated after the Microbicides 2002 meeting.