Ulipristal acetate: New fibroid treatment?
Ulipristal acetate: New fibroid treatment?
Ulipristal acetate, the drug recently approved as an emergency contraceptive in the United States (Ella, Watson Pharmaceuticals, Morristown, NJ), is being eyed for other gynecologic uses. In research looking at women with symptomatic fibroids who were planning to undergo surgery, treatment with the selective progesterone-receptor modulator was effective in controlling excessive bleeding and reducing fibroid size at 13 weeks.1,2
Fibroids, also known as uterine leiomyomas, are the most common benign uterine tumors in women of reproductive age.3 In addition to anemia caused by heavy bleeding, fibroids can cause pelvic pain, pressure, dysmenorrhea, reduced quality of life, and infertility. While most fibroids are treated with surgical or radiologic interventions, options for medical therapy are limited.
Which women might best benefit from medication management of uterine fibroids? Two groups come to mind, says lead investigator of the two trials, Jacques Donnez, MD, PhD, professor at the Cliniques Universitaires Saint-Luc Catholic University of Louvain in Brussels, Belgium. They are:
- all women suffering from menorrhagia due to the presence of myomas;
- the large group of women (ages 40-50) with large myomas.
The goal is to avoid hysterectomy, says Donnez. Fibroids remain the leading cause of the surgical procedure.4
Take a closer look
The recently published research includes two investigations.
One of the investigations is a placebo-controlled dose-ranging trial.1 The other is a noninferiority trial comparing the same two doses of ulipristal acetate with injections of leuprolide, a gonadotropin-releasing hormone (GnRH). Leuprolide is considered the most effective medical therapy available for fibroid treatment.5
Both studies included premenopausal women, ages 18-50, with symptomatic fibroids, including heavy menstrual bleeding who were eligible for hysterectomy. In addition to heavy menstrual bleeding, patients in the dose-finding trial had to be anemic; all women in the investigation received concomitant oral administration of iron.
In the dose-finding trial, both 5 mg and 10 mg daily doses were highly effective in reducing menstrual blood loss. Researchers report about 75% of women treated with ulipristal acetate became amenorrheic.1
In the trial looking at ulipristal acetate and leuprolide, control of excessive bleeding was more rapid in patients receiving ulipristal acetate than in those receiving leuprolide. Median times to amenorrhea were seven days for patients receiving 5 mg ulipristal acetate, compared to five days for those receiving 10 mg of the drug and 21 days for those receiving leuprolide.
In the investigation looking at ulipristal acetate and leuprolide, women could elect to have surgery following their 13-week treatment course. All treatments reduced the volume of the three largest fibroids; median reductions were seen at week 13 in 36% of the 5 mg ulipristal acetate group, compared to 42% of the 10 mg ulipristal acetate group and 53% of the group receiving leuprolide. For those patients who did not undergo hysterectomy or myomectomy, researchers noted that ulipristal acetate had a more sustained effect on the reduction of fibroids volume during the six months follow up without further treatment than did leuprolide acetate.2
Investigators noted no major safety concerns with ulipristal acetate during the 13-week trial; it had little impact on serum estrogen levels and bone markers, and it did not cause hot flashes. While nonphysiologic endometrial changes associated with progesterone-receptor modulators occurred in almost two-thirds of women receiving ulipristal acetate during their treatment, such changes resolved six months following discontinuation of the study drug.2
The profound hypoestrogenism associated with GnRH agonist administration represents a major disadvantage in treating symptomatic fibroids, notes Andrew Kaunitz, MD, professor and associate chair in the Obstetrics and Gynecology Department at the University of Florida College of Medicine — Jacksonville. "Although the endometrial changes associated with current use of ulipristal acetate appear to be benign, the endometrial safety of this class of medications will not be resolved until longer-term studies are conducted," Kaunitz notes.
What's the next step?
PregLem, a Swiss-based specialty biopharmaceutical subsidiary of Hungarian-based pharmaceutical manufacturer Gedeon Richter, recently has received positive feedback from the European Medicines Agency in seeking European marketing authorization of the drug. Trademarked as Esmya, it will be used in pre-operative treatment of uterine fibroids.
There remains a substantial need for effective medical therapy of fibroids, according to an editorial accompanying the two published studies.6 Findings of the two trials point not only to a role for ulipristal acetate in preoperative treatment but, with more study, a possible effective long-term or intermittent medical approach to treating selected patients with symptomatic fibroids, says Kaunitz.
References
- Donnez J, Tatarchuk TF, Bouchard P, et al. Ulipristal acetate versus placebo for fibroid treatment before surgery. N Engl J Med 2012; 366:409-420.
- Donnez J, Tomaszewski J, Vázquez F, et al. Ulipristal acetate versus leuprolide acetate for uterine fibroids. N Engl J Med 2012; 366:421-432.
- Wallach EE, Vlahos NF. Uterine myomas: an overview of development, clinical features, and management. Obstet Gynecol 2004; 104:393-406.
- Walker CL, Stewart EA. Uterine fibroids: the elephant in the room. Science 2005; 308:1,589-1,592.
- Lethaby A, Vollenhoven B, Sowter M. Pre-operative GnRH analogue therapy before hysterectomy or myomectomy for uterine fibroids. Cochrane Database Syst Rev 2001:CD000547.
- Stewart EA. Uterine fibroids and evidence-based medicine — not an oxymoron. N Engl J Med 2012; 366:471-473.
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