Elinzanetant for the Treatment of Vasomotor Symptoms Associated With Menopause: A Phase 3 Randomized Clinical Trial.

IMPORTANCE

There is an unmet need for long-term, safe, effective, and hormone-free treatments for menopausal symptoms, including vasomotor symptoms (VMS) and sleep disturbances.

OBJECTIVE

To evaluate the 52-week efficacy and safety of elinzanetant, a dual neurokinin-targeted therapy, for treating moderate to severe VMS associated with menopause.

DESIGN, SETTING, AND PARTICIPANTS: OASIS-3 was a double-blind, placebo-controlled, randomized phase 3 clinical trial that was conducted at 83 sites in North America and Europe from August 27, 2021, to February 12, 2024, and included postmenopausal women aged 40 to 65 years who were seeking treatment for moderate to severe VMS (no requirement for a minimum number of VMS events per week). The data were analyzed on March 11, 2024.

INTERVENTION

Once-daily oral elinzanetant, 120 mg, or matching placebo for 52 weeks.

MAIN OUTCOMES AND MEASURES

The primary outcome was mean change from baseline to week 12 in the frequency of daily moderate to severe VMS, which was analyzed using a mixed model with repeated measures. Secondary end points included changes over 52 weeks in measures evaluating sleep disturbance and the effect on menopause-related quality of life. Exploratory end points included mean changes over 50 weeks in frequency and severity of daily moderate to severe VMS. Exploratory and secondary end points were analyzed using descriptive statistics. Safety was also assessed.

RESULTS

Overall, 313 women (mean [SD] age, 54.6 [4.7] years; 51 [16.3%] were Black or African American, and 240 [76.7%] were White individuals; 34 [10.9%] were Hispanic or Latina) were randomized to receive elinzanetant and 315 (mean [SD] age, 54.9 [5.0] years; 44 [14.0%] Black or African American, 34 [10.8%] Hispanic or Latina, and 253 [80.3%] White individuals) to receive placebo. At week 12, the mean change from baseline in daily moderate to severe VMS frequency was -5.4 (95% CI, -6.3 to -4.5) for elinzanetant and -3.5 (95% CI, -4.1 to -2.9) for placebo; the least-squares mean difference for elinzanetant vs placebo was -1.6 (95% CI, -2.0 to -1.1; P < .001). Although no statistical hypotheses were defined, nor was the study powered to detect between-group differences for the secondary and exploratory end points, descriptive analyses showed numerical advantages for elinzanetant vs placebo for improving VMS frequency and severity over 50 weeks and sleep disturbances and menopause-related quality of life over 52 weeks. Regarding safety, elinzanetant was not associated with hepatotoxic effects, endometrial hyperplasia, or meaningful changes in bone density or bone turnover markers. Treatment-related adverse events were more common with elinzanetant than placebo (30.4% vs 14.6%); the most frequent were somnolence, fatigue, and headache.

CONCLUSIONS AND RELEVANCE

The OASIS-3 randomized clinical trial expanded on findings from the 26-week OASIS-1 and OASIS-2 trials, exploring the use of elinzanetant over a longer duration and in a broader population. Elinzanetant shows promise as a treatment for moderate to severe VMS.

TRIAL REGISTRATION

ClinicalTrials.gov Identifier: NCT05030584.