Elinzanetant for menopause-associated sleep disturbance: pooled analysis of two phase III studies

This study aimed to evaluate the effects of elinzanetant on sleep in postmenopausal women with vasomotor symptoms (VMS), including by symptom burden. Pooled phase III OASIS-1 and OASIS-2 data included postmenopausal women aged 40–65 years experiencing ≥50 moderate-to-severe VMS/week, randomized to elinzanetant 120 mg (n = 399) or placebo (n = 397). Sleep disturbance was assessed using the Patient-Reported Outcomes Measurement Information System Sleep Disturbance Short Form (PROMIS SD SF) 8b and the Insomnia Severity Index (ISI). Changes from baseline to week 12 were analyzed using mixed models for repeated measures. At week 12, elinzanetant showed greater reductions from baseline versus placebo in PROMIS SD SF 8b T-score (least squares [LS] mean difference: −4.9; 95% confidence interval [CI] − 6.0, −3.9; nominal p < 0.0001) and ISI (LS mean difference: −3.0; 95% CI −3.7, −2.2, nominal p < 0.0001). Larger reductions occurred in women with higher baseline insomnia and VMS frequency. Improvements were evident by week 1 (PROMIS SD SF 8b LS mean difference versus placebo: −4.7; 95% CI −5.7, −3.8; nominal p < 0.0001). By week 12, 67% of women on elinzanetant versus 47% on placebo were within the normal PROMIS range. Elinzanetant produced rapid-onset improvements in sleep disturbance that were sustained at week 12, supporting its potential to treat menopause-associated sleep disturbance in women with VMS. Many women going through menopause experience hot flashes and sleep disturbance that impact their quality of life. Elinzanetant is a recently approved hormone-free treatment that blocks two receptors in the brain (neurokinin-1 and neurokinin-3), thereby reducing hot flashes. This article investigates how elinzanetant affects sleep, combining data from two large clinical trials (OASIS-1 and OASIS-2). A total of 796 postmenopausal women who suffered from frequent, moderate-to-severe hot flashes took either elinzanetant 120 mg once daily for 26 weeks (n = 399) or a placebo for 12 weeks followed by elinzanetant for 14 weeks (n = 397). Women’s sleep quality was assessed using questionnaires called the PROMIS Sleep Disturbance Short Form 8b (where higher scores mean worse sleep) and the Insomnia Severity Index, as well as night-time awakenings recorded by the Hot Flash Daily Diary. Most women had moderate levels of sleep disturbance and insomnia at the start of the study. After 12 weeks, women taking elinzanetant had greater improvements in sleep than those taking placebo, with more than twice the benefits seen on the PROMIS sleep scores, which represented a clinically meaningful difference. Similar benefits were seen on the insomnia severity scale. Women with moderate or severe sleep disturbance improved into the mild or normal range. Improvements in sleep started early within the first week of treatment and were observed across the overall population of women taking elinzanetant in the study. These results suggest that elinzanetant is a rapid-acting option for improving sleep disturbance in women with menopause-associated hot flashes.