Asoprisnil is a novel selective
progesterone receptor modulator that exhibits partial agonist and antagonist activities in animals and humans. It demonstrates a high degree of
progesterone receptor specificity and tissue selectivity. Although
asoprisnil at high doses exhibited some antiglucocorticoid activity in animal models, no antiglucocorticoid effects were observed at therapeutic doses in humans. In male rats,
asoprisnil showed mixed androgenic and antiandrogenic properties. Unlike antiprogestins,
asoprisnil at high doses exhibited only marginal labor-inducing activity in guinea pigs during midpregnancy and was completely ineffective in inducing preterm parturition. In nonhuman primates,
asoprisnil completely eliminated menstrual cyclicity and induced endometrial
atrophy. Early clinical studies of
asoprisnil in healthy volunteers demonstrated a dose-dependent suppression of menstruation, irrespective of the effects on ovulation, with no change in basal
estrogen concentrations and no
breakthrough bleeding. Phase 2 studies in subjects with
uterine fibroids demonstrated that
asoprisnil induced
amenorrhea and reduced the volume of the dominant
leiomyoma in a dose-dependent manner without altered basal
estrogen and with virtually no clinical symptoms of
estrogen deprivation.
Asoprisnil seems to exhibit a direct inhibitory effect on both the endometrium and
leiomyoma. In all studies to date,
asoprisnil has maintained a favorable safety and tolerability profile. Thus,
asoprisnil has the potential to target the major clinical symptoms of leiomyomata related to both
menorrhagia and the size of the
tumors and may, therefore, reduce or eliminate the need for surgery.