Asoprisnil -: Endometriosis therapy treatment of uterine fibroids selective progesterone receptor modulator

The development of selective progesterone receptor modulators (SPRMs) resulted from a program focused on the discovery of compounds which could interact with the progesterone receptor without inducing the side effects of progesterone agonists and antagonists. The goal was to identify agents with antiproliferative effects on the endometrium and breast, without interfering with ovarian estrogen secretion and its protective effects on bone and the cardiovascular system. In the course of the drug discovery program, the progesterone receptor binding affinity and agonist and antagonist activity of a number of compounds were tested and compared to those of progesterone antagonists. In these experiments, asoprisnil demonstrated the greatest progesterone-agonist effects and the lowest progesterone-antagonist effects; it is now the SPRM furthest along in clinical development. In phase II clinical trials in patients with uterine fibroids, once-daily oral asoprisnil was found to reduce the size of fibroids and decrease symptoms, while controlling excessive bleeding. Adverse events were mild and estradiol levels unaffected. The agent is currently undergoing phase III investigation in patients with uterine fibroids. In another phase II study, asoprisnil demonstrated efficacy in reducing nonmenstrual pelvic pain and dysmenorrhea in women with endometriosis and was well tolerated.