Two studies demonstrate effectiveness of PregLem's Esmya as uterine fibroid treatment

PregLem SA's Esmya (ulipristal acetate), an orally active selective progesterone receptor modulator, appears to be efficacious in the treatment of uterine fibroids before surgery, according to two Phase III trials. The PEARL I trial involved approximately 240 women with symptomatic fibroids, excessive uterine bleeding and anemia who were randomized to receive Esmya 5 mg/day, Esmya 10 mg/d or placebo for as long as 13 weeks. All of the patients received iron supplementation. The...

PregLem SA's Esmya (ulipristal acetate), an orally active selective progesterone receptor modulator, appears to be efficacious in the treatment of uterine fibroids before surgery, according to two Phase III trials.

The PEARL I trial involved approximately 240 women with symptomatic fibroids, excessive uterine bleeding and anemia who were randomized to receive Esmya 5 mg/day, Esmya 10 mg/d or placebo for as long as 13 weeks. All of the patients received iron supplementation. The co-primary efficacy endpoints were the percentage of patients with a reduction in uterine bleeding (a score of less than 75 on the pictorial blood-loss assessment chart) at week 13 and the change in total fibroid volume at week 13.

At the end of the treatment period, uterine bleeding was controlled in 91 percent of the women in the Esmya 5 mg treatment arm, in 92 percent of those in the Esmya 10 mg arm and in 19 percent of those treated with placebo. The difference between active treatment and placebo was statistically significant for both doses of Esmya.

Amenorrhea was reported in 73 percent, 82 percent and 6 percent of the respective treatment groups, with amenorrhea occurring within 10 days in the majority of the patients who received Esmya. Median changes in total fibroid volume were reductions of 21.2 percent and 12.3 percent in the Esmya 5 mg and 10 mg arms, respectively, and an increase of 3 percent in the placebo group. Again, for both comparisons, the difference between Esmya and placebo was statistically significant at both dose levels.

The study authors noted that Esmya induced benign histologic endometrial changes that resolved by six months after treatment ended. One patient in the Esmya 10 mg group experienced uterine hemorrhage during treatment, and one patient in the placebo group had a fibroid protruding through the cervix.

In the PEARL II study, Esmya at dosages of 5 mg/d and 10 mg/d was shown to be noninferior to monthly injections of Abbott's Lupron Depot (leuprolide acetate), a gonadotropin-releasing hormone agonist, in controlling uterine bleeding in women with symptomatic uterine fibroids before planned surgery. Esmya also had a better side-effect profile.

The double-blind, noninferiority trial included 307 patients who were randomized to receive three months of daily therapy with Esmya or monthly intramuscular injections of Lupron Depot at a dose of 3.75 mg. The main efficacy endpoint was the proportion of patients with controlled uterine bleeding at week 13, with a prespecified noninferiority margin of 20 percent.

Uterine bleeding was controlled in 90 percent of the patients who were treated with Esmya 5 mg, in 98 percent of those who received Esmya 10 mg and in 89 percent of those treated with Lupron Depot.

Median times to amenorrhea were seven days for the patients who received Esmya 5 mg, five days for those who received Esmya 10 mg and 21 days for those who received Lupron Depot. The difference between Esmya 10 mg and placebo was statistically significant.

Significantly more patients in the Lupron Depot group than in the Esmya 5 mg and 10 mg groups reported experiencing moderate to severe hot flashes (40 percent, 11 percent and 10 percent, respectively). The difference between active treatment and placebo was statistically significant for both doses of Esmya.

PregLem, a wholly owned subsidiary of Gedeon Richter Plc, funded the studies, which were published in the Feb. 2 issue of The New England Journal of Medicine.

In December 2010, Watson Laboratories Inc. entered into an exclusive licensing agreement with PregLem to develop and market Esmya, a potential first-in-class, orally active selective progesterone receptor modulator, in the United States and Canada.

This information concerns a use that has not been approved by the Food and Drug Administration.