The United Kingdom government-funded international Microbicide Development Programme (MDP) is dropping one of the two potential vaginal microbicides it was planning to take into full-scale clinical trials, due to start next year in a number of African countries. Although this is already the largest single medical research project that the Department for International Development has ever funded, additional funding guarantees are still needed to ensure the trial is carried through to completion.
The original idea was to compare dextrin-2-sulphate, also known as Emmelle, from ML Laboratories, with PRO 2000 from Indevus Pharmaceuticals and with a placebo gel. HIV-negative women taking part in the trial would agree to use one of the three gels along with condoms and would be followed up to compare rates of HIV infection, expected to occur when some women are unable to use condoms but may still be using that gel. Both substances are technically fusion inhibitors, which prevent HIV entering target cells, though they cannot be used as treatment drugs. They are inexpensive to make and have been developed by small biotechnology companies under agreements to ensure future access for public sector use in developing countries.
The main reason for the decision to drop Emmelle is that in laboratory studies, it is substantially less effective than PRO 2000 in blocking HIV infection. There had also been concerns that the two substances were too similar to each other and to several other microbicides that are being taken into full-scale testing. ML Laboratories has said that as the product could not be taken forward without public-sector support for trials, it will terminate all work on it and focus its resources elsewhere. In the short term, ML Laboratories will benefit from this move.
The MDP trial will still have three arms, but will now compare two doses of PRO 2000 (0.5mg and 2mg), which is also due to be tested at an even higher dose in another trial. This offers the possibility of information about the relationship between dose and protection which could be of great value for the development of future microbicides. Alternatively, if the low dose is as effective as the higher doses tested, it would reduce the cost of mass manufacture and speed access to an effective product.
The grant allocated to the MDP by the Department for International Development is £16 million, which is now understood to be less than half of what will ultimately be needed to complete the trial. With at least 12,000 women to be recruited and supported for 9 months or longer, and many more who would need to be tested for HIV and referred, where necessary, to treatment services, the logistics of the whole enterprise are a major challenge. Extensive feasibility studies including clinical trials using both Emmelle and PRO 2000 have already begun and the trial organisers hope to begin enrolment around April 2005.
Note: at the time of writing, the Microbicides Development Programme website had not been updated to reflect this development.