This transcript has been edited for clarity.
Hello. I am Dr. JoAnn Pinkerton, professor of obstetrics and gynecology at the University of Virginia and a North American Menopause Society–credentialed menopause specialist.
I am excited to tell you about a brand-new, just-approved non-estrogen therapy for treatment of menopausal symptoms.. The manufacturer, Astellas, is expected to make fezolinetant available at pharmacies before the end of this year. This medication binds to and blocks the neurokinin 3 (NK3) receptor, which plays a role in regulating body temperature, leading to a reduction in hot flashes.
For women suffering from frequent moderate to severe hot flashes, fezolinetant is an exciting breakthrough in women’s health as it is a highly effective nonhormonal treatment that reduces hot flashes and improves quality of life.
In two phase 3 clinical trials (Johnson et al. and Lederman et al.), fezolinetant 45 mg reduced the frequency of vasomotor symptoms by about 65%, significantly more than placebo, and similar to the 75% reduction seen with hormone therapy. Fezolinetant’s efficacy becomes evident within 1 week, reducing both frequency and severity of hot flashes.
With respect to side effects, 1%-2% of the menopausal women participating in clinical trials reported adverse events, including headaches, abdominal pain, diarrhea, insomnia, back pain, hot flushes, and reversible elevated hepatic transaminases. Serious adverse events were infrequent.
Subgroup analysis of data presented at ACOG’s 2023 annual meeting noted fezolinetant’s effectiveness among diverse populations, including White or Black race, body mass index of 30 or higher, those younger or older than age 55, smokers, former smokers, and never smokers, in U.S. as well as in European trial participants.
With respect to safety, a 52-week placebo-controlled safety trial confirmed safety for this time period. Adverse effects on the endometrium were neither seen nor expected, as fezolinetant is a centrally acting non–estrogen-containing medication. In addition, no loss of bone density was seen.
Prior trials of neurokinin receptor antagonists suggested the potential for hepatotoxicity. Increases in ALT or AST noted in one of the phase 3 trials of fezolinetant were described as asymptomatic, isolated, intermittent, or transient and returned to baseline during treatment or after discontinuation. However, the FDA placed a warning about liver injury potential. Package labeling recommends baseline liver function tests before starting fezolinetant and at 3, 6, and 9 months. In addition, concomitant use of moderate CYP1A2 inhibitors, including many antidepressants and cimetidine, should be avoided.
As with other recently approved medications, I am concerned that high cost could prevent appropriate candidates from having access.
Until now, the FDA had approved only one nonhormone therapy for vasomotor symptoms, 7.5 mg paroxetine salt. However, neither this formulation nor off-label use of other SSRIs, SNRIs, gabapentinoids, oxybutynin, or clonidine are as effective as hormone therapy or fezolinetant for moderate to severe vasomotor symptoms.
For women with bothersome menopausal hot flashes who can’t or choose not to use hormone therapy, including those with estrogen-sensitive breast or uterine cancers, fezolinetant offers a much-needed, highly effective, safe, nonhormone/non-estrogen option to treat their hot flashes.
The FDA approved it for treating vasomotor symptoms of menopause (hot flashes and night sweats) but it also appears to improve sleep disruption, mood, and quality of life.
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