Elinzanetant for menopause-associated vasomotor symptoms: pooled analysis of two phase III trials

This study aimed to evaluate the vasomotor symptoms (VMS) efficacy profile of elinzanetant (dual neurokinin-1 and neurokinin-3 receptor antagonist). Data were pooled from the phase III 26-week (12-week placebo-controlled) OASIS-1 and OASIS-2 trials, enrolling naturally/surgically postmenopausal women aged 40–65 years with ≥50 moderate-to-severe VMS per week, randomized to elinzanetant 120 mg (n = 399) or placebo (n = 397). Descriptive statistics summarized the mean VMS frequency change and proportion of participants achieving ≥75% reductions. Mixed models for repeated measures estimated least-squares (LS) mean differences between elinzanetant and placebo for mean change in VMS frequency over time, by subgroups (race/ethnicity/body mass index/smoking history) and at daytime/night-time. Two days after treatment initiation, greater VMS frequency reductions were observed with elinzanetant versus placebo. The LS mean difference in VMS frequency versus placebo from baseline to Week 1 was −2.03 (95% confidence interval: −2.75, −1.31; nominal p < 0.0001); reductions were maintained through Week 12. By Week 12, 50.7% of elinzanetant versus 25.2% of placebo participants achieved ≥75% reduction in VMS frequency. Greater mean reductions in VMS frequency were consistently observed with elinzanetant versus placebo across subgroups and at daytime/night-time. Elinzanetant led to rapid, sustained reductions in VMS frequency versus placebo, consistent across diverse subgroups and at daytime/night-time, with a high proportion of treatment responders, indicating broad effectiveness for VMS treatment. Hot flashes are common, disruptive menopause symptoms. Elinzanetant is a neurokinin-targeted therapy investigated for hot flash treatment in two clinical trials, OASIS-1 and OASIS-2, where it resulted in fewer hot flashes than placebo. Here, we further assessed elinzanetant’s effects on hot flashes by pooling results from both trials. Both trials recruited postmenopausal women aged 40–65 years suffering from 50+ moderate-to-severe hot flashes per week. Overall, 399 women were given elinzanetant 120 mg for 26 weeks, and 397 were given placebo for 12 weeks followed by elinzanetant for 14 weeks. Changes in number of hot flashes over time, at daytime/night-time and in different groups of women (e.g. race/ethnicity/body mass index/smoking history), as well as the number of women responding to treatment, were studied. Within 2 days after beginning treatment, the number of hot flashes was more markedly reduced with elinzanetant than placebo; this reduction was maintained throughout the study. By Week 12, at least 75% of hot flashes were reduced in around half of elinzanetant participants compared to a quarter of placebo participants. Elinzanetant reduced the average number of hot flashes more than placebo, regardless of women’s race/ethnicity/body mass index/smoking history or whether VMS occurred at daytime/night-time. In summary, elinzanetant led to rapid reductions in the number of hot flashes compared to placebo, with a high proportion of women responding to treatment. This was consistent across diverse groups of women and at daytime/night-time, suggesting that elinzanetant could be a suitable treatment option for hot flashes in a broad range of women.