Breakthrough in Menopause Treatment: Elinzanetant Cuts Hot Flashes and Enhances Sleep, New Trials Reveal

In two pivotal Phase 3 clinical trials, Elinzanetant showed statistically significant reductions in the frequency and severity of vasomotor symptoms compared to placebo. Additionally, Elinzanetant notably improved sleep disturbances and menopause-related quality of life while maintaining a favorable safety profile. The findings were published online in JAMA.

Elinzanetant, a selective neurokinin-1,3 receptor antagonist, targets key pathways to regulate body temperature and mood, providing a new option for managing menopause-related vasomotor symptoms such as hot flashes and night sweats. These symptoms can significantly impact the quality of life, affecting daily activities and sleep patterns.

Considering the need for safe and effective nonhormonal treatments for menopausal VMS, JoAnn V. Pinkerton, University of Virginia Health, Charlottesville, and colleagues aimed to evaluate the safety and efficacy of elinzanetant for the treatment of moderate to severe menopausal vasomotor symptoms.

Two randomized, double-blind Phase 3 trials, OASIS 1 and OASIS 2, evaluated the efficacy of Elinzanetant in postmenopausal women aged 40 to 65 years with moderate to severe vasomotor symptoms. OASIS 1 was conducted at 77 sites across the US, Europe, and Israel from August 27, 2021, to November 27, 2023, while OASIS 2 took place at 77 sites in the US, Canada, and Europe from October 29, 2021, to October 10, 2023. Participants received either 120 mg of oral Elinzanetant daily for 26 weeks or a matching placebo for 12 weeks, followed by 14 weeks of Elinzanetant.

The primary outcomes assessed were the mean changes in the frequency and severity of moderate to severe vasomotor symptoms from baseline to weeks 4 and 12, as recorded in the electronic hot flash daily diary. Secondary outcomes included changes in the Patient-Reported Outcomes Measurement Information System Sleep Disturbance Short Form 8b total T score and the Menopause-Specific Quality of Life questionnaire total score from baseline to week 12.

The researchers reported the following findings:

• Eligible participants (mean age, OASIS 1: 54.6 years; OASIS 2: 54.6 years) were randomized to elinzanetant (OASIS 1: n = 199; OASIS 2: n = 200) or placebo (OASIS 1: n = 197; OASIS 2: n = 200). 78.0% and 81.0% completed OASIS 1 and 2, respectively.
• For the elinzanetant and placebo groups, the baseline mean VMS per 24 hours was 13.4 versus 14.3 (OASIS 1) and 14.7 versus 16.2 (OASIS 2).
• Baseline VMS severity was 2.6 versus 2.5 (OASIS 1) and 2.5 versus 2.5 (OASIS 2).
• Elinzanetant significantly reduced VMS frequency at week 4 (OASIS 1: −3.3; OASIS 2: −3.0) and week 12 (OASIS 1: −3.2; OASIS 2: −3.2).
• Elinzanetant also improved VMS severity at week 4 (OASIS 1: −0.3; OASIS 2: −0.2) and week 12 (OASIS 1: −0.4; OASIS 2: −0.3).
• Elinzanetant improved sleep disturbances and menopause-related quality of life at week 12, and the safety profile was favorable.

"Elinzanetant offers the potential as a well-tolerated and effective nonhormonal treatment to meet the unmet needs of many menopausal individuals suffering from moderate to severe vasomotor symptoms," the researchers concluded.

Reference:

Pinkerton JV, Simon JA, Joffe H, et al. Elinzanetant for the Treatment of Vasomotor Symptoms Associated With Menopause: OASIS 1 and 2 Randomized Clinical Trials. JAMA. Published online August 22, 2024. doi:10.1001/jama.2024.14618