Elinzanetant, a once-daily oral neurokinin-1 and neurokinin-3 receptor antagonist, reduced moderate to severe vasomotor symptoms at 12 weeks compared with placebo in a phase 3 randomized controlled trial of postmenopausal patients.
In the OASIS-3 trial, patients receiving elinzanetant reported a mean reduction of 5.4 daily hot flashes at week 12, compared with 3.5 among those who received placebo. This equated to a 74% reduction with elinzanetant vs 47% with placebo. Improvements were observed within the first week. By week 50, mean daily frequency was 1.4 with elinzanetant and 3.5 with placebo.
The trial enrolled 628 postmenopausal patients aged 40 to 65 years at 83 sites in North America and Europe. Patients were randomized to elinzanetant (n = 313) or placebo (n = 315). The mean age was 55 years. The study was conducted from August 2021 to February 2024.
The primary endpoint was change in daily moderate to severe vasomotor symptoms (VMS) frequency from baseline to week 12. Secondary outcomes included sleep disturbance and menopause-related quality of life over 52 weeks. Exploratory analyses assessed durability of treatment effect and VMS severity.
In this phase 3 trial, elinzanetant reduced vasomotor symptoms at 12 weeks compared with placebo and showed sustained improvements over 1 year. The drug was generally well tolerated and not associated with hepatotoxicity, endometrial changes, or bone loss. Sleep disturbance scores improved by week 52, with greater reductions in the elinzanetant group. Menopause-related quality-of-life scores also improved.
Adverse events were reported in 70% of patients receiving elinzanetant and 61% of those receiving placebo. The most common were somnolence, fatigue, and headache. Serious adverse events occurred in 4% of the elinzanetant group and 2% of the placebo group; none were attributed to treatment. Discontinuations due to adverse events were more frequent with elinzanetant.
No cases of endometrial hyperplasia, endometrial cancer, or hepatotoxicity were observed. Bone mineral density changes at 1 year were consistent with expected age-related loss and did not differ between groups.
The study had limitations. Asian and Pacific Islander patients were underrepresented, limiting generalizability. The trial was not powered to detect statistical differences in sleep disturbance or quality-of-life measures. Patients with recent cancer histories were excluded, so findings may not apply to this population.
“As women may experience disruptive menopausal symptoms for multiple years, this study aimed to fulfill the need for longer-term evaluation of hormone-free alternative treatments for VMS,” said Nick Panay, MBBS, BSc, of Queen Charlotte’s & Chelsea Hospital, Imperial College London, and colleagues.
Full disclosures can be found in the study.
Source: JAMA Internal Medicine
