Millions of women experience disruptive menopause symptoms annually, including vasomotor symptoms (VMS) like hot flashes and night sweats, which affect up to 80% of women. Sleep disturbances are also prevalent, impacting overall quality of life and cognitive function. Existing treatments, such as hormone therapy and antidepressants, have limitations including contraindications, safety concerns, and tolerability issues, leaving a significant unmet need.
Emerging neurokinin-targeted therapies (NKTs) offer a new non-hormonal approach. These therapies target the KNDy neurons in the hypothalamus, which become overactive during menopause due to declining estrogen levels. Drugs like elinzanetant, a dual NK1 and NK3 receptor antagonist, and fezolinetant, a mono NK3 receptor antagonist, work by modulating neurokinin signaling. Clinical trials, including the OASIS program for elinzanetant and SKYLIGHT for fezolinetant, have demonstrated significant reductions in VMS frequency and severity. Elinzanetant has also shown consistent improvements in sleep disturbances.
Elinzanetant has demonstrated a favorable safety profile across multiple trials, with no significant hepatotoxicity signals, endometrial pathology, or bone density changes observed. While generally well-tolerated, headache, fatigue, and somnolence were reported more frequently. Fezolinetant carries warnings regarding potential liver injury and requires monitoring.
NKTs are also proving beneficial for women undergoing endocrine therapy (ET) for hormone receptor-positive breast cancer, a group particularly susceptible to severe VMS. Elinzanetant has shown efficacy and a consistent safety profile in this population, leading to its inclusion as a preferred non-hormonal option in NCCN guidelines for managing VMS in breast cancer patients on ET. These advancements provide much-needed therapeutic options for women facing disruptive menopause symptoms across various life stages and medical conditions.