Safety and tolerability of elinzanetant: a pooled analysis from four randomized clinical trials

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.

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.

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.

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.

Bayer.