Elinzanetant, a novel dual neurokinin-1,3 receptor agonist, met all key primary and secondary endpoints in 2 pivotal phase 3 studies, demonstrating statistically significant reductions in the frequency and severity of moderate to severe vasomotor symptoms (VMS) associated with menopause.
The topline findings, from the OASIS 1 and OASIS 2 clinical trials, were announced on January 8 by pharmaceutical giant Bayer and included improvement of disturbances in sleep and menopause-related quality of life. The safety profile of the nonhormonal elinzanetant observed in both studies was generally consistent with data previously published on the compound.
Up to 80% of women report VMS during the menopausal transition, Bayer said, and more than one-third report severe symptoms, some lasting a decade or more beyond the last menstrual period. Symptoms are triggered by falling estrogen levels that lead to hyperactivation of a woman’s thermoregulatory pathway, and are a primary reason for clinical visits during this phase of life.
“Menopausal symptoms such as hot flashes and sleep disturbances can be highly disruptive and broadly impact health and quality of life, still many women cope in silence and remain untreated,” JoAnn Pinkerton, MD, professor and director of Midlife Health at UVA Health in Charlottesville, VA, said in the Bayer statement. “It’s important that we continue to research for solutions that address the unmet needs of women, and I am looking forward to the unveiling of the full results.”
Elinzanetant is the first dual antagonist targeting both NK-1 and NK-3 receptors and is administered orally once daily. The compound’s purported mechanism of action, modulation of estrogen-sensitive hypothalamic KNDy neurons that hypertrophy with estrogen depletion, could explain the impact on moderate to severe VMS as well as improvements observed in sleep disruption, according to the company.
The safety and efficacy of elinzanetant were evaluated in the OASIS 1 and 2 (NCT05042362 and NCT05099159) phase 3 studies. Both trials are part of the 4-study OASIS clinical development program, studies 1-3 evaluating elinzanetant 120 mg vs placebo against VMS caused by menopause and OASIS 4 against VMS caused by endocrine therapy for breast cancer.
There were 396 participants in OASIS 1 and 400 in OASIS 2, all aged 40 to 65 years. In addition to significant reductions in frequency and severity of VMS from baseline at study weeks 4 and 12, investigators reported statistically significant changes in the 3 key secondary endpoints, ie, reduction in VMS frequency from baseline to week 1, decreased sleep disturbance and improvement in menopause-related quality of life, compared to placebo.
The number of women experiencing menopause is projected to increase to 1.2 billion globally by 2030, with as many as 47 million women entering this life phase annually, according to Bayer. The decline in hormonal activity that typically occurs during women’s late 40s or early 50s can provoke symptoms that significantly affect health, quality of life, utilization of health care, and productivity at work. The most common and disturbing of these are VMS, sleep disturbance and mood changes.
“We are excited about the positive results of these two pivotal Phase III studies for elinzanetant, reinforcing its potential as a non-hormonal treatment option in menopause management,” Christian Rommel, PhD, Bayer AG executive vice president, global head of research and development and member of the executive committee of Bayer AG’s Pharmaceutical Division, concluded in the statement.