A Phase 3 clinical study demonstrates that the investigational nonhormonal compound fezolinetant for menopause-related hot flashes is safe.
Results of the Phase 3 SKYLIGHT 4™ clinical study were presented on October 13 at the North American Menopause Society Annual Meeting.
Developed by Astellas Pharma Inc., fezolinetant is an investigational oral, nonhormonal compound for treating moderate to severe vasomotor symptoms (VMS). Characterized as hot flashes and/or night sweats, VMS are common symptoms of menopause.
The Phase 3 SKYLIGHT 4™ study included 1,800 women with VMS at over 180 sites within the US, Canada, and Europe. 52-week-long research looked at the safety and tolerability of fezolinetant taken at 30 and 45 mg once daily.
"Based on our initial assessment, we are pleased with the outcome of the SKYLIGHT 4 study, which further characterizes the long-term safety of fezolinetant," said Nancy Martin, MD, PharmD, Vice President, Global Medical Head, Medical Specialties, Astellas. "With these fezolinetant data, we are hopeful that we will have the opportunity to deliver a first-in-class, nonhormonal treatment option for moderate to severe VMS associated with menopause."
The drug's developer says that reported treatment-emergent adverse events (TEAEs) were generally mild or moderate, with the most common being headache and COVID-19. The incidence of TEAEs was similar in the fezolinetant and placebo groups.
Moreover, researchers found that the frequency of elevated liver enzymes was low across groups, and elevations were generally asymptomatic and resolved on treatment or soon after study drug discontinuation.
Patricia Weiser, PharmD, a Pennsylvania-licensed pharmacist, says that an increase in liver enzymes is not an uncommon side effect of medications, and levels typically return to normal after stopping the medication. It does not necessarily indicate liver damage; instead, it can be a temporary sign that the liver is stressed.
"However, medicines that stress the liver may not be as safe for people with pre-existing liver problems," Weiser said.
To date, the only non-hormone treatment for hot flashes approved by the US Food and Drug Administration (FDA) is paroxetine, which is included in the class of selective serotonin reuptake inhibitors (SSRIs).
Weiser, PharmD, says there is not enough data yet to compare fezolinetant to paroxetine.
"But, having another nonhormonal treatment option would be beneficial for women looking for some relief, especially for those who can't take or don't want to take paroxetine," she said to Healthnews.
To alleviate menopause symptoms, menopause hormone therapy (MHT) can be applied. However, treatment is associated with an elevated breast and uterine cancer risk.
Reducing the quality of life
About 60-80% of American women experience VMS at some point during the menopausal transition, according to the Study of Women's Health Across the Nation (SWAN), which included 3,302 midlife women who were followed for more than ten years. Of those, African American women are most likely to report VMS.
Hot flashes are also associated with a poorer quality of life. The SWAN study linked VMS to sleep disturbance, depression, lower bone mineral density, and a higher risk of cardiovascular disease.
The National Institute of Aging (NIA) recommends lifestyle changes to improve hot flashes, such as avoiding alcohol, spicy foods, and caffeine, quitting smoking, maintaining a healthy weight, and exploring mind-body practices.