Vasomotor symptoms (VMS), or hot flashes, are reported by up to 80% of women during the menopausal transition and are the leading cause of medical attention during the transition. More than one-third of women report severe symptoms, which last, on average, seven years but can last ten years or more after the last period, with ethnic and racial variation. Vasomotor symptoms have been shown to negatively impact sleep, mood, and quality of life and affect workplace productivity and relationships at work and home.
Elinzanetant is a dual neurokinin (NK1, NK3) receptor antagonist in late-stage clinical development. Data show statistically significant effects on the triad of hot flashes, mood, and sleep. At ACOG 2024, attendees heard the first presentations on the findings from the two pivotal phase 3 clinical trials, OASIS 1 and 2.
These two randomized, blinded trials were conducted over 26 weeks at 184 sites in 15 countries to test the safety and efficacy of elinzanetant. The first 12 weeks were placebo-controlled; the next 14 weeks, all participants were on active treatment. In OASIS 1 and 2, the investigational compound elinzanetant achieved statistically significant reductions in both frequency and severity of VMS at weeks 4 and 12 compared to blinded placebo over 12 weeks compared to placebo.
In addition, the studies showed that elinzanetant met its secondary endpoints, with a statistically significant reduction in VMS frequency from baseline to week one (thus showing a rapid response, which is important to women). Sleep disturbances and menopause-related quality of life were significantly improved compared to placebo, and a favorable safety profile was seen.
Headache and fatigue were the most frequent treatment-related adverse events, which improved over time during the study.
The robust efficacy of elinzanetant in reducing the frequency and severity of VMS seen across multiple trials, along with a favorable safety profile of the drug, reinforces its potential as a nonhormonal treatment for women experiencing distressing VMS associated with menopause. There were no significant abnormal laboratory findings, including liver tests. No incidences of endometrial hyperplasia or malignant neoplasm were identified. No cases of drug-induced liver injury causally related to elinzanetant were seen as assessed by the liver safety monitoring board.
Elinzanetant is a dual neurokinin receptor antagonist (nk1, 3) that blocks neurokinin B signaling in the brain, which leads to decreases in hot flashes in the thermoregulatory zone of the brain. The first Neurokinin 3 receptor antagonist, fezolinetant, was approved in May of 2023 and works primarily on hot flashes, although effects on sleep and mood were found. Neurokinin-1 receptor antagonist is believed to affect sleep and mood, unrelated to its effects on hot flashes. It is a different compound, metabolized differently from fezolinetant, and thus expected to have different efficacy and safety profiles. The hope is that the dual neurokinin receptor antagonist will show additional benefits for hot flashes, sleep, and mood- to allow better treatment of women who have sleep or mood disturbances beyond those due to hot flashes.
The study results shown from OASIS 1 and 2, along with the long-term safety topline results of OASIS 3 released earlier this month on efficacy and safety, suggest the potential of elinzanetant as an effective and safe nonhormonal treatment to provide a much-needed nonhormone treatment for menopausal women. The hope is that it may become a safe and effective option for menopausal women suffering from the triad of moderate to severe VMS, sleep disruption, and decreased menopause-related quality of life.
The topline data released by Bayer of Oasis 3, a 52-week study on the efficacy and safety of Elinzanetant, showed more extended-term safety and efficacy, meeting all study endpoints. We look forward to the results of an ongoing clinical trial, Oasis 4, where participants have either breast cancer or are at high risk for breast cancer, taking tamoxifen or aromatase inhibitors.
Menopausal women who cannot take hormone therapy due to health issues such as estrogen-sensitive breast cancer, stroke, heart disease, or venous thrombosis, or choose not to take it, need more therapeutic options for burdensome VMS, which have been shown to affect workplace productivity and relationships at work and home.
For women who take these neurokinin receptor antagonists for hot flashes, it is important to remember that they won’t reap the benefits of estrogen in the prevention of bone loss, lipids, and on vaginal health, and these will need to be addressed separately.
Dr. Pinkerton has reported financial ties with Bayer Pharmaceuticals.
Image by Peanut
