Benign prostatic hyperlasia — KMD-3213
Enlargement of the prostate is very common in older men, with half of those over 60 and 90% of over-85s being affected. It causes problems with urination, as the growing gland obstructs the neck of the bladder, and can have a knock-on effect on the kidneys. A non-cancerous enlarged prostate is not in itself dangerous, but if impaired kidney function or other complications arise, then it needs to be addressed.
Treatment is either prostatectomy or with drugs, either α-blockers or the drug finasteride (Merck & Co's Proscar). α1-Adrenoceptor antagonists relax the smooth muscle in the wall of the urethra, improving urine flow, whereas finasteride works by inhibiting the conversion of testosterone to its more active metabolite 5-dehydroxytestosterone, reducing the androgenic stimulation of the prostate. Several α-blockers are in use, notably prazosin and terazosin, both of which are fairly unselective, leading to side effects because of their vascular effects. Newer compounds such as tamsulosin have improved selectivity, and hence lower incidences of these unwanted side effects.
A number of more selective α1-adrenoceptor antagonists are now in development. Among these is KMD-3213, which was discovered by Japanese company Kissei and has been licensed to Daiichi Pharmaceutical for Phase III work. In vivo studies in rats showed the compound to be highly selective for the a1-adrenoceptors in prostate tissue, rather than the α1B and α1D adrenoceptors that predominate in the vascular system.1 A range of functional experiments confirmed its selectivity.2
Further studies in rats have shown it to have higher selectivity and a longer duration of action than prazosin, terazosin or tamsulosin.3 An investigation has been carried out in healthy volunteers to establish the optimal dosing regimen.4 The compound is currently undergoing Phase II trials in the US, following the successful completion of Phase II trials in Japan.