Menopausal VMS Severity, Frequency Reduced Significantly with Elinzanetant: Bayer Shares Data from Pivotal OASIS 1 and 2 Trials

Elinzanetant, a novel dual neurokinin-1,3 (NK-1, NK-3) receptor antagonist, met all key primary and secondary endpoints in 2 pivotal phase 3 clinical trials, demonstrating statistically significant reductions in the frequency and severity of moderate to severe vasomotor symptoms (VMS) associated with menopause, according to an announcement from developer Bayer.¹

Data from the company’s OASIS 1 and OASIS 2 trials were presented during a late-breaking clinical trials session at the 2024 American College of Obstetricians and Gynecologists annual meeting, May 17-19, in San Francisco.¹

JoAnn Pinkerton, MD
Women's Health, UVA

In both trials, elinzanetant also met 3 key secondary endpoints: statistically significant reductions in VMS frequency from baseline to week 1 and improvement in both sleep disturbance and quality of life compared to placebo in postmenopausal women aged 40 to 65 years.¹

Elinzanetant is the first dual antagonist targeting both NK-1 and NK-3 receptors and is administered orally once daily.

“There are limited approved nonhormonal treatments for bothersome menopausal symptoms, such as hot flashes and sleep disturbances. Consequently, many women experience discomfort for months or even years, with the majority of symptoms left untreated,” said JoAnn Pinkerton, MD, professor, director of midlife health at UVA Health, in Charlottesville, VA. “These results are exciting news for women who suffer from moderate to severe hot flashes and build on our confidence that elinzanetant may be a potential nonhormonal solution for them.”¹

In the pivotal OASIS 1 and 2 trials, the novel agent met all 4 primary endpoints providing statistically significant improvements in moderate to severe VMS from baseline to week 4 and to week 12 vs placebo.

“There are limited approved nonhormonal treatments for bothersome menopausal symptoms, such as hot flashes and sleep disturbances. Consequently, many women experience discomfort for months or even years, with the majority of symptoms left untreated.”

Among elinzanetant-treated participants in OASIS 1 (N = 396), significant mean reductions vs placebo were reported for VMS frequency at week 4 (-3.29) and week 12 (-3.22) and for severity at week 4 (-0.33) and week 12 (-0.40) (P < .001 for all).¹

In OASIS 2 (N = 400), researchers reported significant mean reductions with elinzanetant vs placebo for VMS frequency at week 4 (-3.04; P < .001) and at week 12 (-3.24; P < .001) and for VMS severity at week 4 (-0.22; P =.0003) and at week 12 (-0.29; P < .001). Headache and fatigue were the most frequent treatment emergent adverse events among participants treated with elinzanetant in both studies, part of a safety profile otherwise described as "favorable." ¹

Bayer also reported statistically significant outcomes for the 3 key secondary endpoints across OASIS 1 and 2, showing reductions in the frequency of VMS from baseline to week 1 (P < .001 and P = .001, respectively), improvements in sleep disturbances (P < .001 in both studies) and menopause-related quality of life (P < .001 and P =.006, respectively) compared to placebo.¹

“The robust efficacy and favorable safety profile of elinzanetant reinforces its potential as a non-hormonal treatment for women experiencing menopause,” Christian Rommel, PhD, member of the Executive Committee of Bayer AG’s Pharmaceutical Division and Global Head of Research and Development, said in the announcement. “We look forward to submitting applications to health authorities for marketing authorizations of elinzanetant to treat moderate to severe VMS associated with menopause, building upon our extensive legacy and commitment to women’s healthcare.”¹

OASIS development program

In OASIS 1 and OASIS 2, conducted at 184 sites in 15 countries, participants in the elinzanetant arm received a 120 mg dose of elinzanetant once daily for 26 weeks and patients in the control arm received a matching placebo once daily for 12 weeks, followed by elinzanetant 120 mg dose for 14 weeks.¹

In March, Bayer announced positive topline results for the double-blind, randomized, placebo-controlled multicenter phase 3 OASIS 3 trial (N = 628), investigating the efficacy and long-term safety of elinzanetant for the treatment of VMS.² The study successfully met the primary endpoint with a statistically significant reduction in the frequency of moderate to severe vasomotor symptoms from baseline to week 12 vs placebo.2 The company reported the safety profile of elinzanetant observed over 52 weeks in this study is “overall consistent with previously conducted studies and published data.”¹

The full long-term data from OASIS 3 will be presented at an upcoming scientific meeting, according to the statement. Those findings will join OASIS 1 and 2 data in upcoming regulatory submissions.¹

References
1. Elinzanetant significantly reduces frequency and severity of moderate to severe hot flashes associated with menopause. News release. Bayer. May 16, 2024. Accessed May 17, 2024. https://www.bayer.com/media/en-us/elinzanetant-significantly-reduces-frequency-and-severity-of-moderate-to-severe-hot-flashes-associated-with-menopause/
2. Jennings S. Topline phase 3 data release for elinzanetant efficacy for moderate-to-severe VMS. Patient Care. March 19, 2024. https://www.patientcareonline.com/view/topline-phase-3-data-released-for-elinzanetant-efficacy-for-moderate-to-severe-vms