Sonya Collins
FDA approved fezolinetant (Veozah–Astellas Pharma US), a first-in-class neurokinin 3 (NK3) receptor antagonist, for the treatment of moderate to severe vasomotor symptoms (VMS) of menopause in May 2023. Marking an expansion in women’s nonhormonal options for the treatment of these symptoms, fezolinetant is now the second FDA-approved nonhormonal treatment for hot flashes and night sweats, after the SSRI paroxetine (Brisdelle–Noven Pharmaceuticals).
“Despite hormone therapy being the most efficacious treatment of vasomotor symptoms, such as hot flashes, some may be unable or unwilling to use it due to contraindications or perception of risks,” said Nicole Cieri-Hutcherson, PharmD, BCPS, NCMP, a clinical assistant professor at the University at Buffalo School of Pharmacy and Pharmaceutical Sciences, who has a special focus on women’s health. “Unfortunately, efficacious, nonhormonal options are lacking.”
Fezolinetant offers women an additional nonhormonal option.
New drug class
Fezolinetant is an NK3 receptor antagonist. The NK3 pathway regulates the secretion of gonadotropin releasing hormone (GnRH) and plays a role in the brain’s regulation of body temperature and, as a result, the generation of hot flashes. Fezolinetant binds to and blocks the activities of NK3 receptors to prevent hot flashes.
In Phase 3 clinical trials, the most common adverse effect of this drug was headache.
“With earlier medications in the same class, significant elevations in hepatic enzymes were seen,” Cieri-Hutcherson said. “However, with fezolinetant, elevations in hepatic enzymes were rare and resolved either during treatment continuation or treatment discontinuation.”
New, nonhormonal option
Up to 80% of women experience hot flashes during menopause, which can last for several years and have a significant impact on quality of life.
While hormone therapy is the gold standard for treatment of VMS, those who have a history of vaginal bleeding, stroke, heart attack, blood clots, or liver disease are not candidates for this medication. Other women may be unwilling to take hormone therapy based on the risks associated with it, which some perceive to be high. Paroxetine, which also comes with risks of adverse effects and interactions as well as contraindications that patients and providers must consider, has been the only FDA-approved nonhormonal option for patients in this population until now.
“Fezolinetant represents an expansion to the efficacious pharmacotherapeutic armamentarium for the management of vasomotor symptoms,” said Cieri-Hutcherson.
It should be noted, however, that while hormone therapy addresses several symptoms of menopause, fezolinetant is only proven effective for treating hot flashes and night sweats.
“Fezolinetant’s impact on mood, genitourinary, sexual, cardiovascular, metabolic, and bone health remain to be seen,” Cieri-Hutcherson said. “Further studies are needed in larger populations to elucidate this.”
Expanding the nonhormonal armamentarium
Fezolinetant joins a small but potentially growing number of evidence-based pharmaceutical and nonpharmaceutical therapies for menopause symptoms.
The North American Menopause Society (NAMS) recently released a position statement on these options developed by an advisory panel of researchers with expertise in nonhormone medical therapy, herbal therapy, behavioral therapy, and lifestyle approaches for VMS. The recommendations were based on their evaluation of all available literature on these therapies since the publication of NAMS’ last position statement in 2015.
In addition to fezolinetant, the panel recommended cognitive behavioral therapy, clinical hypnosis, weight loss, stellate ganglion blockade, SSRIs/serotonin-norepinephrine reuptake inhibitors, gabapentin, and oxybutynin.
Among those approaches for which the panel did not find sufficient evidence were paced respiration, supplements and herbal remedies, cooling techniques, avoiding triggers, exercise, yoga, mindfulness-based intervention, relaxation, suvorexant, soy products, cannabinoids, acupuncture, calibration of neural oscillations, chiropractic interventions, clonidine, dietary modification, and pregabalin.
“The good news for women is that there are many options available for the treatment of bothersome hot flashes, including several nonhormone therapies,” Stephanie Faubion, MD, NAMS medical director, said in a press release. “We also have a better understanding of what is not effective so that women and health care professionals can target therapies that have been proven to work and avoid the wasted time, energy, and expense associated with ineffective or unproven remedies.” ■