Philadelphia—As many as two-thirds of women in the United States have uterine fibroids, although the usually-benign growths are small enough in two-thirds of cases that they cause few problems, according to past reports.
As for the remaining third of women with the hormone-responsive neoplasms, however, uterine fibroids can cause heavy menstruation that can include clots, related iron-deficiency anemia, pain, and discomfort, as well as reproductive issues.
That’s why new therapies to reduce fibroid-associated bleeding are considered so significant. An article in the New England Journal of Medicine points out that elagolix, an oral gonadotropin-releasing hormone antagonist resulting in rapid, reversible suppression of ovarian sex hormones, appears to reduce fibroid-associated bleeding.
Researchers from Thomas Jefferson University and University of Pennsylvania, Philadelphia conducted two identical, double-blind, randomized, placebo-controlled, 6-month phase III trials (Elaris Uterine Fibroids 1 and 2 [UF-1 and UF-2]) to evaluate the efficacy and safety of elagolix at a dose of 300 mg twice daily in women with fibroid-associated bleeding. The industry-funded study included hormonal “add-back” therapy to replace reduced levels of endogenous hormones—in this case that was estradiol, 1 mg, and norethindrone acetate, 0.5 mg, once daily.
Researchers included an elagolix-alone group to assess the effects of add-back therapy on the hypoestrogenic effects of elagolix. Defined as the primary end point was menstrual blood loss of less than 80 mL during the final month of treatment and at least a 50% reduction in menstrual blood loss from baseline to the final month.
Undergoing randomization to receive either elagolix or placebo and included in the analysis were 412 women in UF-1 and 378 women in UF-2, according to the researchers.
The study team reports that criteria for the primary end point were met in 68.5% of 206 women in UF-1 and in 76.5% of 189 women in UF-2 who received elagolix plus add-back therapy, compared with 8.7% of 102 women and 10% of 94 women, respectively, who received placebo (P <.001 for both trials).
In addition, among the women who received elagolix alone, the primary end point was met in 84.1% of 104 women in UF-1 and in 77% of 95 women in UF-2.
The treatment was not without downsides, however. The authors point out that hot flashes in both trials and metrorrhagia in UF-1 occurred significantly more often with elagolix plus add-back therapy than with placebo. They add, however, that hypoestrogenic effects of elagolix, especially decreases in bone mineral density, were attenuated with add-back therapy.
“Elagolix with add-back therapy was effective in reducing heavy menstrual bleeding in women with uterine fibroids,” according to the researchers.
Elagolix, marketed as Orlissa, was first approved by the FDA in 2018 as the first and only oral gonadotropin-releasing hormone antagonist specifically developed for women with moderate-to-severe endometriosis pain. Approved under priority review, it was the first FDA-approved oral treatment for the management of moderate-to-severe pain associated with endometriosis in more than a decade. In 2019, AbbVie announced the submission of a New Drug Application to the FDA for elagolix for the management of heavy menstrual bleeding associated with uterine fibroids in women.
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As for the remaining third of women with the hormone-responsive neoplasms, however, uterine fibroids can cause heavy menstruation that can include clots, related iron-deficiency anemia, pain, and discomfort, as well as reproductive issues.
That’s why new therapies to reduce fibroid-associated bleeding are considered so significant. An article in the New England Journal of Medicine points out that elagolix, an oral gonadotropin-releasing hormone antagonist resulting in rapid, reversible suppression of ovarian sex hormones, appears to reduce fibroid-associated bleeding.
Researchers from Thomas Jefferson University and University of Pennsylvania, Philadelphia conducted two identical, double-blind, randomized, placebo-controlled, 6-month phase III trials (Elaris Uterine Fibroids 1 and 2 [UF-1 and UF-2]) to evaluate the efficacy and safety of elagolix at a dose of 300 mg twice daily in women with fibroid-associated bleeding. The industry-funded study included hormonal “add-back” therapy to replace reduced levels of endogenous hormones—in this case that was estradiol, 1 mg, and norethindrone acetate, 0.5 mg, once daily.
Researchers included an elagolix-alone group to assess the effects of add-back therapy on the hypoestrogenic effects of elagolix. Defined as the primary end point was menstrual blood loss of less than 80 mL during the final month of treatment and at least a 50% reduction in menstrual blood loss from baseline to the final month.
Undergoing randomization to receive either elagolix or placebo and included in the analysis were 412 women in UF-1 and 378 women in UF-2, according to the researchers.
The study team reports that criteria for the primary end point were met in 68.5% of 206 women in UF-1 and in 76.5% of 189 women in UF-2 who received elagolix plus add-back therapy, compared with 8.7% of 102 women and 10% of 94 women, respectively, who received placebo (P <.001 for both trials).
In addition, among the women who received elagolix alone, the primary end point was met in 84.1% of 104 women in UF-1 and in 77% of 95 women in UF-2.
The treatment was not without downsides, however. The authors point out that hot flashes in both trials and metrorrhagia in UF-1 occurred significantly more often with elagolix plus add-back therapy than with placebo. They add, however, that hypoestrogenic effects of elagolix, especially decreases in bone mineral density, were attenuated with add-back therapy.
“Elagolix with add-back therapy was effective in reducing heavy menstrual bleeding in women with uterine fibroids,” according to the researchers.
Elagolix, marketed as Orlissa, was first approved by the FDA in 2018 as the first and only oral gonadotropin-releasing hormone antagonist specifically developed for women with moderate-to-severe endometriosis pain. Approved under priority review, it was the first FDA-approved oral treatment for the management of moderate-to-severe pain associated with endometriosis in more than a decade. In 2019, AbbVie announced the submission of a New Drug Application to the FDA for elagolix for the management of heavy menstrual bleeding associated with uterine fibroids in women.
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