Prostate disease and the pharmaceutical industry

Medicines for BPH in the development pipeline

There appears to be relatively little activity with new alpha-1 blockers in the clinical trial pipeline, though Abbott has one, ABT-980, in Phase 3. Pfizer’s doxazosin consists of a 50:50 mixture of two different forms called S and R. The US company Sepracor has produced one of these two, S-doxazosin, in pure form. This may have fewer side effects than doxazosin and a Phase 1 clinical trial has now started to test this theory.

Of the 5-alpha reductase inhibitors, only finasteride is licensed in the UK for BPH. This medicine is very effective, but it was shown some years ago that it only reduced the amount of DHT in the blood by about 70 per cent. The reason for this relates to the existence of a second 5-alpha reductase enzyme (Type 1) which generates the other 30 per cent. This raises the question as to whether the Type 1 enzyme plays a part in prostate enlargement.

One way to test this would be to develop a medicine that inhibits both Type 1 and Type 2 enzymes. This has been achieved by Glaxo Wellcome scientists with a compound called GI-198745, which reduces total DHT levels by up to 95 per cent. It has now entered Phase 3 clinical trials which will show whether or not it is an advance in treatment. Even if it is not, it will enable scientists to gain a better understanding of the role of the two kinds of 5-alpha reductase in prostate enlargement, and hence provide other avenues for research.