Elinzanetant is a safe and effective non-hormone treatment for vasomotor symptoms and sleep disturbances associated with menopause.
Hormone therapy is the most effective treatment for vasomotor symptoms (VMS) associated with menopause; however, many women cannot take it due to contraindications or avoid it due to personal preferences. Hence, there is a need for effective non-hormone therapies. Neurokinin (NK)-3 and NK-1 receptors have been associated with the etiology of menopausal VMS and sleep disruptions.
A study in the journal Menopause assessed the efficacy and safety of elinzanetant, a selective NK-1,3 receptor antagonist, for treating menopausal VMS, and examined the drug’s impact on sleep and quality of life (QOL).
Study Design and Population
Phase 2b of the trial involved 199 postmenopausal females between the ages of 40 and 65 years who reported seven or more moderate-to-severe episodes of VMS on a daily basis. They were randomized to elinzanetant 40 (n = 31), 80 (n = 17), 120 (52), or 160 (n = 52) mg or placebo (n = 47) once daily for 12 weeks and followed up for an off-treatment 4-week period.
Significant Reductions in Mean Daily VMS Frequency With Elinzanetant
There were significant and clinically relevant reductions (improvements) in the mean daily VMS frequency with elinzanetant 120 mg from week 4 (p < 0.001) to week 12 (p = 0.01) vs. placebo. Significant improvements were observed with the administration of elinzanetant 160 mg at week 4 (p = 0.01); however, no significant improvements were noted at week 12. Improvements with 40 mg and 80 mg were not significant.
Significantly improved VMS frequency was achieved by week 1 for both 120 mg and 160 mg. Reductions in the mean weekly VMS severity followed a similar trend; however, these were only significant for elinzanetant 160 mg at week 12.
Elinzanetant Improves Sleep and Menopause-Specific QOL
Reductions in the night-time awakening frequency due to VMS were significantly greater vs. placebo for elinzanetant 120 mg at weeks 1 through 8, but not at week 12. Significant improvement in Insomnia Severity Index score was observed for 120 mg and 160 mg elinzanetant at weeks 4 and 12, and 80 mg at week 12. There were statistically significant improvements in the Pittsburgh Sleep Quality Index score for 120 mg and 160 mg at weeks 4 and 12. Improvement in the overall Menopause-Specific QOL questionnaire (intervention version) scores was statistically significant for 120 mg and 160 mg at weeks 4 and 12. Improvements in VMS frequency, sleep, and QOL returned to baseline 4 weeks after treatment discontinuation.
Elinzanetant Is Well-Tolerated With No Concerning Adverse Events
Elinzanetant was well tolerated, with no treatment-emergent adverse events (TEAEs) of concern at any doses tested. There were no significant variations observed in the occurrence of TEAEs across the different treatment groups, however a slightly higher incidence of somnolence was observed for elinzanetant 160 mg and 40 mg. Overall, TEAEs were reported in 67.8% and 60% of participants in the elinzanetant and placebo groups, respectively. In the elinzanetant treatment group, 4.6% of participants experienced adverse events that led to treatment discontinuation, while in the placebo group, this figure was 2%. Notably, there were no instances of treatment discontinuation due to adverse events observed in the 120-mg dosage group. There were sporadic increases in transaminases during treatment that were deemed clinically irrelevant.
These findings suggest that 120 mg elinzanetant offers significant efficacy for treating menopause-related symptoms with a favorable benefit/risk profile.
Simon, J. A., Anderson, R. A., Ballantyne, E., Bolognese, J., Caetano, C., Joffe, H., Kerr, M., Panay, N., Seitz, C., Seymore, S., Trower, M., Zuurman, L., & Pawsey, S. (2023). Efficacy and safety of elinzanetant, a selective neurokinin-1,3 receptor antagonist for vasomotor symptoms: a dose-finding clinical trial (SWITCH-1). Menopause, 30(3), 239–246. https://doi.org/10.1097/gme.0000000000002138