OASIS: Nonhormonal elinzanetant improves hot flashes, menopause-related quality of life
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Key takeaways:
- Elinzanetant reduced hot flash frequency and severity at weeks 4 and 12 compared with placebo.
- Women reported improved sleep and menopause-related quality of life.
Once-daily oral elinzanetant was well tolerated and improved moderate to severe vasomotor symptom frequency and severity, sleep disturbances and menopause-related quality of life, according to results of two studies published in JAMA.
Data from the OASIS studies were first presented at the ACOG Clinical & Scientific Meeting in May.
“Elinzanetant is a nonhormonal compound in development for the treatment of vasomotor symptoms associated with menopause that specifically target both NK1 and NK3 receptors,” JoAnn V. Pinkerton, MD, MSCP, professor of obstetrics and gynecology and director of midlife health at the University of Virginia Health System in Charlottesville and executive director emeritus of The Menopause Society, and colleagues wrote. “Based on clinical data, it was hypothesized that the dual inhibition of NK1 and NK3 receptors would reduce vasomotor symptoms and may have an effect on sleep disturbances associated with menopause.”
Reduced hot flash frequency, severity
For OASIS 1 and 2, researchers conducted two phase 3 randomized, placebo-controlled studies evaluating the safety and efficacy of elinzanetant (Bayer) to treat moderate to severe vasomotor symptom associated with menopause. All participants were postmenopausal women aged 40 to 65 years (mean age, 54.6 years) with moderate to severe vasomotor symptoms from August 2021 to November 2023 (OASIS 1) and October 2021 to October 2023 (OASIS 2). Researchers randomly assigned participants once-daily oral elinzanetant 120 mg for 26 weeks (OASIS 1, n = 199; OASIS 2, n = 200) or placebo for 12 weeks (OASIS 1, n = 197; OASIS 2, n = 200) and, after 12 weeks, all participants received elinzanetant 120 mg for another 14 weeks.
Primary outcome was mean change in frequency and severity of moderate to severe vasomotor symptoms from baseline to 4 and 12 weeks. Secondary outcomes included sleep disturbances menopause-related quality of life from baseline to 12 weeks, assessed via questionnaires.
Overall, 78% of participants completed OASIS 1 and 81% completed OASIS 2.
In OASIS 1 and 2, baseline mean vasomotor symptoms per 24 hours for women who received elinzanetant were 13.4 and 14.7, respectively, and baseline vasomotor symptom severity was 2.6 and 2.5, respectively.
Elinzanetant reduced vasomotor symptom frequency at 4 and 12 weeks in both OASIS 1 (–3.3 and –3.2) and 2 (–3 and –3.2) compared with placebo (P < .001 for all). During both OASIS studies, women treated with elinzanetant also reported improved vasomotor symptom severity at 4 weeks (–0.3 and –0.4; P < .001 for both) and 12 weeks (–0.2 and –0.3; P < .001 for both) compared with placebo.
Researchers observed improvement in reported sleep disturbances (P < .001 for all) and menopause-related quality of life at 12 weeks in OASIS 1 (P < .001) and OASIS 2 (P = .0059) among women treated with elinzanetant vs. placebo.
Adverse events were similar in the treatment and placebo groups in both trials. Headache and fatigue were the most frequently reported adverse events in the elinzanetant groups; there were no incidences of liver toxicity.
“Elinzanetant has the potential to provide a well-tolerated and efficacious nonhormonal treatment option to address the unmet health needs of many menopausal individuals with moderate to severe vasomotor symptoms,” the researchers wrote.
Learning ‘who will benefit the most’
In a related editorial, Stephanie S. Faubion, MD, MBA, NCMP, IF, director of the Mayo Clinic Center for Women’s Health and medical director of The Menopause Society, and Chrisandra L. Shufelt, MD, MS, FACP, NCMP, chair of the division of general internal medicine and senior consultant at the Mayo Clinic Women’s Health and associate director of the Women’s Health Research Center at Mayo Clinic, noted more studies are required to evaluate the full potential of elinzanetant.
“Additional subgroup analyses of these trial results may identify differential benefits of these drugs by age, BMI, race and ethnicity or other factors such that patient stratification based on better-than-average clinical response could facilitate individualization of therapy,” Faubion and Shufelt wrote. “This, in turn, could also influence payer reimbursement strategies to ensure that the individuals who will benefit the most will have access to the medications that can improve their health and quality of life.”
Reference:
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The publication of the results of the OASIS 1 and 2 randomized clinical trials this week is another affirmation of the value of neurokinin receptor antagonists in the treatment of hot flashes. For the “non-menopause practitioners” reading this, do not feel you are totally out of date: the first major publications on the topic of “Menopause and the human hypothalamus: evidence for the role of kisspeptin/neurokinin B neurons in the regulation of estrogen negative feedback,” by Naomi Rance and others only started appearing in 2009. It is amazing to me that in only 15 years, we already have one approved neurokinin-3 receptor antagonist, and now we have favorable results on a neurokinin-1 and -3 receptor antagonist — with data showing sleep improvements as well as hot flash amelioration.
The neurokinin receptor antagonists have significant efficacy on reduction of hot flashes, with elinzanetant also showing sleep improvement. Not only are they effective, but they also act relatively quickly. Most clinicians know that patients today not only want significant improvements in their quality of life, but they also want rapid results. The side effects from these medications are also minimal.
With these favorable results, some have asked if we should use these medications for typical menopause patients with vasomotor symptoms. Unfortunately, neurokinin receptor antagonists, while excellent for hot flashes, do not take care of the genitourinary symptoms of menopause; nor do they help with dry skin, achiness and the myriad of symptoms that many menopausal women experience. However, for women who are experiencing significant vasomotor symptoms and either cannot take estrogens or do not want to take estrogens, they offer very significant help.
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