Fezolinetant vs. elinzanetant for vasomotor symptoms in menopausal women

Both fezolinetant and elinzanetant appear to be associated with beneficial outcomes in menopausal women with vasomotor symptoms, according to a new meta-analysis published in Obstetrics & Gynecology. However, elinzanetant may provide a larger effect size in vasomotor symptom frequency and severity reduction and greatly improved sleep quality compared with fezolinetant.Researchers analyzed the efficacy and safety of fezolinetant and elinzanetant for vasomotor symptoms in menopausal women by systematically searching MEDLINE, EMBASE, and Cochrane through until Aug. 22, 2024. The team limited their investigation to only RCTs comparing fezolinetant and elinzanetant with placebo for vasomotor symptoms in menopausal women.“Our findings indicate that both drugs significantly improve vasomotor symptoms and the quality of life in menopausal women. Additionally, we found that fezolinetant and elinzanetant can improve sleep quality, although elinzanetant has greater effects for this purpose,” said study co-author Artur Menegaz de Almeida, a fourth-year medical student at Federal University of Mato Grosso, Sinop, Brazil.The researchers extracted the number of patients, mean age, body mass index (BMI), and number of patients who underwent oophorectomy. The analysis included seven RCTs with 4,087 patients. The researchers found that fezolinetant and elinzanetant were associated with diminished vasomotor symptom frequency. Fezolinetant 30 mg reduced vasomotor symptom frequency (mean difference 2.16), fezolinetant 45 mg reduced symptoms (mean difference 2.54), and elinzanetant 120 mg reduced symptoms (mean difference 2.99). Both agents showed a decrease in vasomotor symptom severity (fezolinetant 30 mg (mean difference 0.20), fezolinetant 45 mg (mean difference 0.24), and elinzanetant 120 mg (mean difference 0.36)). Elinzanetant 120 mg showed a significant improvement in sleep quality (mean difference 4.65). Elinzanetant 120 mg was associated with the occurrence of drug-related adverse events (11.70% fezolinetant vs 20.75%, risk ratio [RR] 0.57) and headache (2.54% fezolinetant vs 8.0%, RR 0.32).“In our opinion these findings are clinically relevant and point to more personalized medicine, as both drugs have their own particularities that should be taken into consideration during prescribing. Further clinical trials assessing neurokinin inhibitors are needed to advance research in non-hormonal agents for reducing vasomotor symptoms in menopausal women,” said Menegaz de Almeida.Fezolinetant is an oral non hormonal NK3 antagonist for treating moderate and severe vasomotor symptoms related to menopause. Elinzanetant is a dual NK1 and NK3 inhibitor, and it has also been assessed for the same purpose. Of the 4,087 included patients, 2,252 (55.10%) received fezolinetant, 399 (9.72%) received elinzanetant, and 1,436 (35.13%) received a placebo.In this patient population, treatment needs to be individualized based on patient-specific factors such as the severity of vasomotor symptoms and the presence of insomnia because climacteric syndrome presents heterogeneously. The authors note that this study has several limitations because there were slight differences between the included RCTs in terms of administered dose and most of the participants were white. Dr. Corinne Bazella, professor and a Menopause Society Certified physician at Case Western Reserve University School of Medicine in Cleveland, Ohio, said the key question is: does the blocking of the neurokinin 1 receptor that occurs in elinzanetant but not fezolinetant contribute to this observation? “More studies are needed as the number of patients who got elinzanetant is lower than the number of patients who got fezolinetant. Fezolinetant was studied in differing doses, and the two were not directly compared,” said Dr Bazella. If more studies are conducted with more patients and the better sleep quality is proven with elinzanetant, then possibly patients with worse sleep could choose this medication, said Dr. Bazella. However, efficacy is not the only factor in deciding what medication patients choose. “Side effects, risk of adverse effects, cost, and insurance coverage are also taken into consideration. If both are covered equally, which in Canada is possible, then possibly patients with more sleep difficulties would choose elinzanetant over fezolinetant. However patients struggling with headaches may choose to use fezolinetant over elinzanetant.” Dr. JoAnn V. Pinkerton, professor of Obstetrics and Gynecology and director Midlife Health the University of Virginia, Charlottesville, said the findings in this current meta analysis are surprising with fezolinetant appearing superior to elinzanetant. However, she noted there were some fundamental study design issues, such as not including phase 2 trials in the fezolinetant data and combining data for two doses of fezolinetant. Further, the phase 2 trial data was not included for elinzanetant. “It is crucial to include all relevant data in a meta analysis to ensure comprehensive research. In addition, the differences in vasomotor symptom frequency and sleep disturbances were not adequately addressed. These issues led to findings that do not necessarily reflect the differences between the two medications shown in clinical trial publications,” Dr. Pinkerton told the Medical Post.In addition, the meta analysis did not address the rare adverse events of liver issues and the recommendation for frequent monitoring for liver safety for fezolinetant. Liver issues have not been seen in the elinzanetant trials. “While the meta-analysis suggests fezolinetant as a potential first-line option for mild to moderate vasomotor symptoms, it's important to note that the meta-analysis does not fully support this conclusion. The studies did not include participants with mild hot flashes, only those with more than 50 moderate to severe hot flashes per week, and there were no head-to-head trials for comparison,” said Dr. Pinkerton.When striving to deliver personalized care, it's crucial to understand the unique mechanisms of action of the two neurokinin receptor antagonists. “This understanding will aid physicians in selecting the most suitable treatment for their patients. Both fezolinetant and elinzanetant are effective for hot flashes, but elinzanetant, in particular, has not shown any signs of liver toxicity and seems to have additional benefits for sleep and mood,” said Dr. Pinkerton.References:Menegaz de Almeida A, Oliveira A, Lopes Lucca P, et al. Fezolinetant and Elinzanetant Therapy for Menopausal Women Experiencing Vasomotor Symptoms A Systematic Review and Meta-analysis Obstetrics & Gynecology 145(3):p 253-261, March 2025. | DOI: 10.1097/AOG.0000000000005812

Fezolinetant vs. elinzanetant for vasomotor symptoms in menopausal women

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