BACKGROUND AND PURPOSE:

• Elagolix is a GnRH antagonist that causes rapid, reversible suppression of ovarian sex hormones
  • It may reduce fibroid-associated bleeding
• Schlaff et al. (NEJM, 2020) conducted two phase 3 trials to assess the efficacy and safety of elagolix for heavy menstrual bleeding due to fibroids

METHODS:

• Two identical, double-blind, randomized, placebo-controlled, 6-month phase 3 trials
  • Elaris Uterine Fibroids 1 and 2 (UF-1 and UF-2)
• Participants
  • Women with fibroid-associated bleeding
• Interventions
  • Elagolix 300 mg twice daily with hormonal “add-back” therapy
    • Estradiol 1 mg, and norethindrone acetate 0.5 mg once daily
  • Elagolix-alone
  • Placebo
• Primary outcome
  • Menstrual blood loss <80 ml during the final month of treatment
  • ≥50% reduction in menstrual blood loss from baseline to the final month

RESULTS:

• 412 women in UF-1 | 378 women in UF-2
• More women who received elagolix plus add-back therapy achieved the primary outcome than did women who received placebo (P<0.0001 for both studies)
  • Elagolix plus add-back therapy
    • UF-1: 68.5%
    • UF-2: 76.5%
  • Placebo
    • UF-1: 8.7%
    • UF-2: 10%
  • Elagolix-alone
    • UF-1: 84.1% 
    • UF-2: 77%
• Comparing elagolix plus add-back therapy vs placebo, the following were increased
  • Hot flushes (in both trials)
  • Metrorrhagia (in UF-1)
• Add-back therapy did improve hypoestrogenic effects of elagolix (e.g., decrease in bone mineral density)
• Low rate of serious adverse events
  • No cases with drug-induced liver injury

CONCLUSION:

• For women with uterine fibroids, elagolix was effective in reducing heavy menstrual bleeding
• The authors state that

Since the trials were designed primarily to compare elagolix plus add-back therapy with placebo and prespecified a comparison of the two elagolix groups only with respect to bone mineral density, we cannot make conclusions regarding elagolix with add-back therapy as compared with elagolix alone with respect to the effects on other outcomes

Learn More – Primary Sources:

Elagolix for Heavy Menstrual Bleeding in Women with Uterine Fibroids

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Another New Drug in the Pipeline to Treat Fibroids

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How does TXA Measure Up as a Treatment for Menorrhagia?

Elaris EM-III and Elaris EM-IV Results: Long-Term Endometriosis Outcomes Following Administration of Elagolix