Oral Ulipristal Proves Highly Effective for Uterine Fibroids

Laura Newman, MA

February 02, 2012

February 2, 2012 — The oral selective progesterone receptor modulator ulipristal proved highly effective as a treatment for symptomatic uterine fibroids, according to  2 studies published online yesterday in the New England Journal of Medicine. In both patient groups, ulipristal rapidly reduced excessive bleeding, reduced the size of uterine fibroids, and was well tolerated.

"This class of drugs has many important uses," independent commentator Jeffrey T. Jensen, MD, MPH, director of the Women’s Health Research Unit, Oregon Health Sciences University, Portland, told Medscape Medical News. "Unfortunately, these anti-progestins have been highly politicized, and it is really sad. Ulipristal is not and has never been an abortifacient."

However, the drug was approved for emergency contraception in 2010. Known as ella (HRA Pharma)  in the United States and ellaOne in Europe, ulipristal works by interrupting ovulation. For emergency contraception, a 30-mg dose is used. By contrast, the newly published studies tested 5-mg and 10-mg daily doses for fibroid treatment.

In the first of the 2 studies, researchers tested the efficacy of 5 mg versus 10 mg of ulipristal against placebo in 242 women aged 18 to 50 years with symptomatic fibroids, excessive uterine bleeding, and anemia. The study took place at 38 academic research centers in Europe and Ukraine between October 2008 and August 2010. The second study was a noninferiority trial comparing ulipristal (5 mg or 10 mg) with once-monthly injections of leuprolide, the current gold standard.

In the placebo-controlled study, Jacques Donnez, MD, PhD, Cliniques Universitaires Saint-Luc Catholic University of Louvain, Brussels, Belgium, and coauthors found that excess menstrual bleeding was controlled in 91% of 96 women taking the 5-mg daily dose, in 92% of 98 women taking the 10-mg dose and 19% of 48 women taking placebo (P ≤ .001). Amenorrhea was highest in the 10-mg group: 82% vs 73% in the 5-mg group and 6% in the placebo group. By using pictorial blood-loss assessment charts to estimate the reduction in bleeding, investigators found median changes on chart scores greater than 300 in both ulipristal groups, whereas there was no change in the placebo group at week 5 to 8 and week 9 to 12 (P < .001). Bleeding control was faster in both groups taking ulipristal: 75% by day 8 vs 6% in the placebo group. Fibroid volume and uterine volume declined at least 25% by week 13 (P = .01 and P < .001, respectively, for women taking the 5-mg dose; P = .01 and P = .006 for women taking the 10-mg dose). Both doses were well tolerated, with 2 exceptions: One patient in the 10-mg group had a uterine hemorrhage, and 1  in the placebo group had fibroid protrusion through the cervix.

In the noninferiority trial, also led by Dr. Donnez, the investigators compared the 5-mg and 10-mg ulipristal doses against leuprolide in 303 randomly assigned patients. Ulipristal controlled bleeding in 98% of women taking 10 mg, 90% taking 5 mg, and 89% receiving leuprolide. In addition, "ulipristal acetate attenuated bleeding more rapidly than leuprolide acetate, with median times to amenorrhea of 7 days in patients receiving 5 mg of ulipristal acetate, 5 days in those receiving 10 mg of ulipristal acetate, and 21 days in those receiving leuprolide acetate," the authors write.

Dr. Jensen summed up the importance of the studies this way: "These are easy-to-use pills and could be an important tool in the medical treatment of fibroids. Not only did they do well against a highly effective gold standard, but they were superior to placebo at 10-mg dose."

The study authors note that one limitation to the trials is that ulipristal treatment was limited to 13 weeks. "Hence, more data are needed regarding benefits and risks of long-term treatment with ulipristal acetate," they write in the discussion of the noninferiority trial.

The study was supported by PregLem. Dr. Donnez disclosed participation in PregLem’s scientific advisory board and payment from stocks sold in October 2010 from the acquisition by Gedeon. Coauthor Dr. Richter and several other co-investigators disclosed other possible sources of conflict with HRA Pharma, Serono, Merck, and other companies. Some of the investigators were employees of PregLem. Dr. Jensen reported consultancies with Bayer, Merck, Abbott, HRA Pharma (France), and the Population Council.

N Engl J Med. 409-420, 421-432.

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