Abstract / Summary
Summary: Background: Elinzanetant is a dual neurokinin (NK)-1 and NK-3 receptor antagonist approved for the treatment of moderate-to-severe vasomotor symptoms (VMS) associated with menopause, or those caused by adjuvant endocrine therapy for breast cancer treatment. Methods: In this pooled safety analysis, safety data were pooled from four randomized, placebo-controlled studies: the phase IIb SWITCH-1 trial (2018–2019) and phase III OASIS-1–3 trials (2021–2024). All four studies were multicentre, multinational, double-blind trials that included postmenopausal women aged 40–65 years experiencing moderate-to-severe VMS due to natural or surgical menopause. Data were analysed exploratively. Assessments included frequency of treatment-emergent adverse events (TEAEs) over 12 and 52 weeks, and exposure-adjusted incidence rates (EAIRs, with 95% confidence intervals [CIs]) over 52 weeks. EAIRs were calculated by weighting event counts against total exposure time (person-years) across studies. Additionally, liver safety and incidence of neoplasms were evaluated. Findings: The 12-week pooled safety analysis set included 1519 participants: 765 participants in the elinzanetant 120 mg group and 754 participants in the placebo group. The 52-week pooled safety analysis set included 1113 participants in the elinzanetant 120 mg group and 754 participants in the placebo group. TEAEs occurred in 50·8% and 43·2% of participants in the elinzanetant 120 mg and the placebo groups, respectively, over 12 weeks; EAIRs were 196·61 (95% CI 181·33–213·18) and 209·00 (95% CI: 188·96–231·15) in the elinzanetant and placebo groups, respectively, over 52 weeks. The most common TEAEs reported with elinzanetant were headache, fatigue, and somnolence. Treatment discontinuation was low with elinzanetant (7·8%) but higher than placebo (3·6%) over 12 weeks; EAIRs were 14·95 (95% CI 11·99–18·62) and 10·96 (95% CI 7·87–15·27), respectively, over 52 weeks. There were no Hy's Law cases or indication of cholestatic injury. EAIRs of malignant tumors had overlapping CIs between treatment groups. No endometrial hyperplasia/malignancy was reported in either group. Interpretation: The overall safety profile of elinzanetant appeared favorable in 1113 women based on this exploratory pooled safety analysis. Future time-to-event analyses of TEAEs and real-world post-marketing data are warranted to better characterize the long-term safety profile of elinzanetant. Funding: Bayer.