Non-hormone drugs can reduce menopausal hot flash frequency, severity

Key takeaways:

• Fezolinetant and elinzanetant were associated with reduced vasomotor symptom frequency and severity.
• Sleep quality and menopause-specific quality of life also improved with use of fezolinetant and elinzanetant.

Fezolinetant and elinzanetant are both promising nonhormone therapies for managing vasomotor symptoms among postmenopausal women, with favorable safety profiles for up to 12 weeks, according to a systematic review published in Menopause.

“Based on the data available, the new FDA-approved neurokinin receptor inhibitor fezolinetant, as well as pipeline medication, elinzanetant, show promising efficacy and a favorable safety profile,” Nicole Cieri-Hutcherson, PharmD, BCPS, MSCP, clinical associate professor at the School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, told Healio. “These agents could be considered in women who have contraindications to or choose not to use hormone therapies for the management of vasomotor symptoms. Preliminary data suggests elinzanetant may have similar clinical utility if approved by the FDA.”

Cieri-Hutcherson and colleagues searched MEDLINE, Embase and International Pharmaceutical Abstracts from inception to March 2023 and identified six randomized controlled trials (RCTs) and one post hoc analysis with data from 3,503 postmenopausal women. All studies assessed the safety and efficacy of fezolinetant (Veozah, Astellas) or elinzanetant (Bayer) — both nonhormone neurokinin-3 receptor antagonists — for managing vasomotor symptoms associated with menopause.

Overall, four RCTs reported on fezolinetant data, two RCTs reported on elinzanetant data and the post hoc analysis reported on a fezolinetant RCT.

At 4 and 12 weeks, three RCTs and the post hoc analysis demonstrated reduced vasomotor symptom frequency with fezolinetant 30 mg and 45 mg, ranging from 50% to 93%, and improved vasomotor symptom severity scores at 12 weeks compared with placebo, the researchers reported. Fezolinetant also was associated with improved sleep quality and Menopause-Specific Quality of Life (MENQOL) scores at 4 and 12 weeks compared with placebo.

All elinzanetant RCTs demonstrated reduced vasomotor symptom frequency and severity, improved sleep quality and improved MENQOL scores with elinzanetant 120/160 mg or 150/300 mg compared with placebo, according to the researchers.

The most reported treatment-emergent adverse events for fezolinetant and elinzanetant were COVID-19, headache, somnolence and dizziness. In addition, liver enzyme elevation incidence was low, asymptomatic and resolved during treatment or after discontinuation across all studies.

According to Cieri-Hutcherson, there is a considerable need for nonhormone alternatives to hormone therapy, and these medications offer more options to treat vasomotor symptom for menopausal women.

“Not included in this systematic review are the results of elinzanetant phase 3 studies, OASIS 1 and 2. In January 2024, Bayer announced that elinzanetant met all four primary outcomes,” Cieri-Hutcherson said. “We should expect that elinzanetant will follow in the path of fezolinetant in seeking FDA approval for the management of vasomotor symptoms. Additional research is needed into the mechanism of vasomotor symptoms and nonhormone options for the management of vasomotor symptoms.”

For more information:

Nicole Cieri-Hutcherson, PharmD, BCPS, MSCP, can be reached at necieri@buffalo.edu.