Elinzanetant: Efficacy and safety in the management of vasomotor symptoms in postmenopausal women, a systematic review and meta‐analysis with grading of recommendations assessment, development, and evaluation assessment

Abstract Background Menopause is frequently associated with different symptoms and signs, such as vasomotor symptoms (VMSs), which can affect women's quality of life. While hormonal therapy is considered the traditional and most used medication for controlling these VMSs associated with menopause, neurokinin (NK) receptor antagonists resemble a novel, promising generation of medications that provide fewer adverse events compared to hormonal therapy. Elinzanetant is the first drug that can act on both NK‐1 and 3 receptors by selectively antagonizing them. It has also been developed for the management of moderate‐to‐severe VMSs. Objectives We aim to investigate the effectiveness and safety of elinzanetant compared to placebo in the management of moderate and severe VMSs that are associated with postmenopausal women. Method We conducted a search of four databases (PubMed, Cochrane, Web of Science, and Scopus) using the following search strategy: ([Elinzanetant) OR [NT‐814] OR [BAY 3427080] OR (NK Receptor Antagonist]) AND ([Menopausal Symptoms] OR [Flashes Vasomotor Symptoms] OR (VMS)) with no search restrictions or filters applied. Selection Criteria We included randomized controlled clinical trials (RCTs) comparing elinzanetant to placebo in post‐menopausal women suffering from frequent moderate‐to‐severe VMSs that reported both efficacy and safety outcomes. We used a uniform Google Sheet designed to collect data from our included RCTs. After data collection, we used Review Manager Software (RevMan) V.5.4.1. to perform all the analyses and plots using a risk ratio (RR) with a 95% confidence interval (CI) for dichotomous outcomes and mean difference (MD) with a 95% CI for continuous outcomes. We conducted risk of bias assessment using Risk of Bias Assessment tool‐2 (ROB2). Results We included five RCTs in our review with 1699 participants. Our results reported that elinzanetant demonstrated a statistically significant difference in reducing both frequency and severity of VMSs at week 4 compared to placebo (MD = −2.75, 95% CI: [−3.83, −1.67], P  < 0.00001; MD = −0.29, 95% CI: [−0.35, −0.22], P  < 0.00001, respectively). These results were maintained at week 12 for both frequency (MD = −2.30, 95% CI: [−3.00, −1.59], P <  0.00001) and severity (MD = −0.35, 95% CI: [−0.43, −0.28], P <  0.00001). Compared to placebo, elinzanetant was associated with a higher incidence of treatment‐emergent adverse events (TEAEs) (RR = 1.12, 95% CI: [1.03, 1.22], P  < 0.01), TEAEs causing permanent discontinuation of the study drug (RR = 2.18, 95% CI: [1.45, 3.28], P  = 0.0002), drug‐related TEAEs (RR = 1.92, 95% CI: [1.53, 2.41], P <  0.00001), headache (RR = 2.19, 95% CI: [1.38, 3.49], P  = 0.0009), somnolence (RR = 2.96, 95% CI: [1.42, 6.17], P  = 0.004), and fatigue (RR = 3.39, 95% CI: [1.77, 6.49], P  = 0.0002). However, no statistically significant difference was observed in the incidence of serious TEAEs (RR = 1.70, 95% CI: [0.82, 3.54], P  = 0.15). Conclusion Elinzanetant showed significant efficacy in reducing both the frequency and severity of VMSs associated with post‐menopausal women at different time points, while concurrently improving outcomes associated with women's quality of life. While elinzanetant was associated with a higher incidence of non‐serious adverse events such as headache, somnolence, and fatigue, which led to more treatment discontinuations, it did not increase the risk of serious adverse events compared to placebo, indicating an acceptable safety profile. Conclusively, our results indicate that elinzanetant represents a promising alternative for VMS management; however, it should not replace the clinical assessment of eligibility for hormone therapy. Further studies are required to confirm its long‐term safety and sustained effectiveness. PROSPERO Registration Our study was registered on PROSPERO on September 20, 2024, with ID CRD42024593052.