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Semin Reprod Med 2004; 22(2): 113-119
DOI: 10.1055/s-2004-828617
Copyright © 2004 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA.

Therapeutic Potential for the Selective Progesterone Receptor Modulator Asoprisnil in the Treatment of Leiomyomata

Kristof Chwalisz1 , Deborah DeManno1 , Ramesh Garg1 , Lois Larsen1 , Cynthia Mattia-Goldberg1 , Therese Stickler1
  • 1Research and Development, TAP Pharmaceutical Products, Inc., Lake Forest, Illinois
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Publication History

Publication Date:
26 May 2004 (online)

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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.

KEYWORDS

Asoprisnil - selective progesterone receptor modulator - leiomyomata - uterine fibroids - uterus

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Kristof ChwaliszM.D. Ph.D. 

TAP Pharmaceutical Products, Inc., 675 N. Field Drive

Lake Forest, IL 60045