IMPORTANCE: Safe and effective nonhormonal treatments for menopausal vasomotor symptoms (VMS) are needed.
OBJECTIVE: To evaluate the efficacy and safety of elinzanetant, a selective neurokinin-1,3 receptor antagonist, for the treatment of moderate to severe menopausal vasomotor symptoms.
DESIGN, SETTING, AND PARTICIPANTS: Two randomized double-blind phase 3 trials (OASIS 1 and 2) included postmenopausal participants aged 40 to 65 years experiencing moderate to severe vasomotor symptoms (OASIS 1: 77 sites in the US, Europe, and Israel from August 27, 2021, to November 27, 2023, and OASIS 2: 77 sites in the US, Canada, and Europe from October 29, 2021, to October 10, 2023).
INTERVENTION: Once daily oral elinzanetant, 120 mg, for 26 weeks or matching placebo for 12 weeks followed by elinzanetant, 120 mg, for 14 weeks.
MAIN OUTCOMES AND MEASURES: Primary end points included mean change in frequency and severity of moderate to severe vasomotor symptoms from baseline to weeks 4 and 12, measured by the electronic hot flash daily diary. Secondary end points included Patient-Reported Outcomes Measurement Information System Sleep Disturbance Short Form 8b total T score and Menopause-Specific Quality of Life questionnaire total score from baseline to week 12.
RESULTS: Eligible participants (mean [SD] age, OASIS 1: 54.6 [4.9] years; OASIS 2: 54.6 [4.8] years) were randomized to elinzanetant (OASIS 1: n = 199; OASIS 2: n = 200) or placebo (OASIS 1: n = 197; OASIS 2: n = 200). A total of 309 (78.0%) and 324 (81.0%) completed OASIS 1 and 2, respectively. For the elinzanetant and placebo groups, the baseline mean (SD) VMS per 24 hours were 13.4 (6.6) vs 14.3 (13.9) (OASIS 1) and 14.7 (11.1) v 16.2 (11.2) (OASIS 2). Baseline VMS severity was 2.6 (0.2) vs 2.5 (0.2) (OASIS 1) and 2.5 (0.2) vs 2.5 (0.2) (OASIS 2). Elinzanetant significantly reduced VMS frequency at week 4 (OASIS 1: -3.3 [95% CI, -4.5 to -2.1], P < .001; OASIS 2: -3.0 [95% CI, -4.4 to -1.7], P < .001) and at week 12 (OASIS 1: -3.2 [95% CI, -4.8 to -1.6], P < .001; OASIS 2: -3.2 [95% CI, -4.6 to -1.9], P < .001). Elinzanetant also improved VMS severity at week 4 (OASIS 1: -0.3 [95% CI, -0.4 to -0.2], P < .001; OASIS 2: -0.2 [95 CI, -0.3 to -0.1], P < .001) and week 12 (OASIS 1: -0.4 [95% CI, -0.5 to -0.3], P < .001; OASIS 2: -0.3 [95% CI, -0.4 to -0.1], P < .001). Elinzanetant improved sleep disturbances and menopause-related quality of life at week 12, and the safety profile was favorable.
CONCLUSIONS AND RELEVANCE: Elinzanetant was well tolerated and efficacious for moderate to severe menopausal VMS.
TRIAL REGISTRATION: ClinicalTrials.gov Identifier: OASIS 1: NCT05042362, OASIS 2: NCT05099159.
| Discipline Area | Score |
|---|---|
| Family Medicine (FM)/General Practice (GP) |  |
| General Internal Medicine-Primary Care(US) | |
| Gynecology | |
| Internal Medicine |  |
Useful information about a new treatment for a problem that significantly impacts QoL for affected individuals. It is helpful to have a precise measurement of the impact of this therapy to share with patients who seek help with these symptoms.
The authors state: “The trials were conducted in accordance with the Declaration of Helsinki […]”, but this research does not strictly comply with “The benefits, risks, burdens and effectiveness of a new intervention must be tested against those of the best proven intervention(s), except in the following circumstances: […]”because, in my opinion, it does not meet either of the two exceptions (no proven intervention or compelling and scientifically sound methodological reasons). Although it was compared against placebo and statistically significant differences are obtained, it should be taken into account whether for a woman with 13-14 menopausal vasomotor symptoms a day (baseline mean), a decrease of 3 menopausal vasomotor symptoms is important. With the placebo, an improvement in quality-of-life was also obtained, a finding similar to that found in other studies, which reinforces the need to test this type of medication against a proven pharmacological alternative.
It is exciting to know that there are additional options soon to become available (hopefully) to effectively reduce both VMS and sleep disturbances in menopausal women.