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• Posted August 22, 2024

Women Could Have New Medical Option to Ease Hot Flashes

A drug under development could provide a much needed option for women seeking relief from hot flashes and other menopausal symptoms, new research shows.

The drug, elinzanetant, cut the frequency of hot flashes by an average of about 56% after one month of use, and by more than 65% after three months.

Overall, about 62% of more than 300 postmenopausal women in two trials experienced "at least a 50% reduction in [hot flash] frequency," wrote a team led by Dr. JoAnn Pinkerton, from University of Virginia Health in Charlottesville.

The drug also appeared to reduce the severity of hot flashes.

The two trials were funded by elinzanetant's maker, Bayer, and published Aug. 22 in the Journal of the American Medical Association. Based in part on these results, the company announced earlier this month that it had filed a new drug application for elinzanetant with the U.S. Food and Drug Administration.

According to Pinkerton's team, up to 80% of women will experience hot flashes -- medically known as menopausal vasomotor symptoms (VSM) -- during menopause, sometimes lasting for many years.

Hot flashes can be debilitating and difficult to predict, and there are few therapeutic options to treat them.

Decades ago, hormone replacement therapy was found to lessen hot flash severity, but further study linked it to a heightened odds for breast cancer and stroke, and many women now avoid the treatment. Certain SSRI antidepressants may help some patients.

However, "many women have contraindications, have tolerability issues leading to discontinuation or prefer not to take these treatments," the study authors noted.

Fezolinetant (Veozah), the first of a new class of non-hormonal drugs called neurokinin (NK)-3 receptor antagonists, gained approval from the U.S. Food and Drug Administration in 2023 for the treatment of moderate to severe hot flashes.

This class of drugs targets a specific type of brain cell called KNDy neurons, known to be involved in the body's "thermoregulation."

The overactivity of KNDy neurons "has been related to disruption of thermoregulation, which may trigger VMS," Pinkerton and her colleagues explained.

Elinzanetant targets this mechanism to help alleviate hot flashes.

The new study includes findings from two phase 3 clinical trials, each involving just over 300 postmenopausal women aged 40 to 65 (the average age was about 55). All had experienced moderate to severe hot flashes.

Women were randomly given either elinzanetant (120 milligrams) or a "dummy" placebo pill to take daily for 26 weeks.

The placebo effect is powerful, so women on either regimen gained some reduction in hot flash frequency and severity.

However, women taking elinzanetant got significantly more relief.

At the start of the trials, the average participant said she suffered through about 14 hot flashes during every 24-hour period.

However, by week 4 of one of the trials, that number had fallen to less than 8 per day among women taking the placebo, and to less than 6 per day among those taking elinzanetant.

By week 12, daily hot flashes had been reduced to less than 8 per day for women taking placebo and to just 4.7 per day for women on elinzanetant.

The latter number represents a 65% reduction in hot flash frequency compared to the beginning of the trial.

When hot flashes did occur they also tended to be less severe for those taking elinzanetant, participants reported. Women taking the drug also reported significant improvement in their sleep, the study authors said.

By the end of both 26-week trials, "more than 80% of participants had achieved at least a 50% reduction" in hot flash frequency, the researchers said, suggesting that the benefits were maintained over the longer term.

As to side effects, about half of participants did complain of issues such as headache or fatigue, Pinkerton's group said. "Most events were of mild intensity, and none were severe," they noted.

"For women that cannot be on hormonal medication -- whether it is medically driven co-morbidities [illnesses], cardiovascular disease, hormone-responsive cancers or other reasons -- this really brings such an area of hope and positivity so that women don't have to suffer," said Dr. Stephanie McNally, director of OB/GYN services at Northwell Health's Katz Institute for Women's Health in Garden City, NY. She was not involved in the new research.

Writing in a journal editorial that accompanied the study, two other experts said these drugs are already entering mainstream practice, with fezolinetant being featured in ads broadcast during this year's Super Bowl.

Drs. Stephanie Faubion and Chrisandra Shufelt, of the Mayo Clinic, noted that drugs targeting the (NK)-3 receptor have already proven effective in easing insomnia.

Therefore, meds like elinzanetant "may work synergistically to inhibit [hot flashes] and improve sleep," they theorized.

There's even a hint from early research that (NK)-3 receptor inhibition could prevent the excess fat deposits around a woman's middle that can come with menopause. So, drugs like fezolinetant and elinzanetant "could also potentially inhibit the known increase in visceral fat associated with the menopause transition," Faubion and Shufelt reasoned.

The bottom line: "With the discovery of non-hormonal treatment options targeting the neurons responsible for VMS, menopause care should advance on this solid scientific footing to benefit affected individuals," the two experts wrote.

More information

Find out more about hot flashes at Cedars-Sinai Los Angeles.

SOURCE: Stephanie McNally, MD, vice president, Northwell OB/GYN Service Line, and director, OB/GYN services, Katz Institute for Women's Health, Garden City, NY; Journal of the American Medical Association, Aug. 22, 2024