This week, drugmaker Bayer published the results of two successful Phase III trials testing its experimental drug elinzanetant as a treatment for hot flashes.
Hot flashes and night sweats are common symptoms of menopause, affecting around 80% of women in their lifetime.
Historically, hot flashes have been effectively treated with hormone therapy, which aims to replace the levels of estrogen and progesterone that decline with menopause.
Women unwilling or unable to use hormones for their hot flashes have had limited other options to date, such as low doses of certain SSRIs.
But in the early 2010s, scientists finally started to unravel some of the mechanisms underlying hot flashes.
Later studies found that blocking the activity of some receptors on these cells could safely reduce hot flashes.
And in May 2023, the Food and Drug Administration approved Astellas Pharma’s fezolinetant, the first drug that treats hot flashes by blocking one of these receptors, NK3.
Across both trials, researchers found that women taking elinzanetant (a once-daily pill) experienced a significant reduction in hot flashes relative to controls.
It appears that a new era in menopausal treatment is approaching. The results of two fruitful Phase III trials evaluating the experimental medication elinzanetant as a hot flash treatment were released this week by the pharmaceutical company Bayer. Right now, the drug is on the verge of being approved globally as the first non-hormonal medication of its kind.
Approximately 80% of women will experience hot flashes and night sweats at some point in their lives as menopausal symptoms. Initially referred to as vasomotor symptoms, hot flashes are defined by sporadic episodes of warmth, redness, and sweating, usually in the face, neck, and chest (night sweats are similar, but they happen at night and during sleep). More severe instances of these episodes are believed to increase the risk of depression and restless nights. These episodes can be extremely uncomfortable. The Mayo Clinic states that although hot flashes do lessen with time, they frequently persist for at least two years and can last up to ten years for certain women.
Hormone therapy, which attempts to restore the levels of progesterone and estrogen that decrease with menopause, has historically been an effective treatment for hot flashes. Large-scale trials started to reveal, however, in the late 1990s, that hormone therapy may increase the risk of heart disease, breast cancer, and stroke in menopausal women. As a result, the treatment quickly saw a significant and long-lasting decline. It’s possible that these risks were exaggerated and that they can be safely reduced, according to more recent studies and data analyses. According to groups such as the North American Menopause Society, most women who begin therapy before the age of sixty and/or within ten years of the last menstrual cycle will benefit from hormonal treatment for hot flashes more than any possible risks. However, hormone therapy is still far less common than it once was, and certain women—such as those who have a history of breast cancer—are more vulnerable to negative side effects.
Low dosages of specific SSRIs are among the few alternatives available to women who are unwilling or unable to use hormones to treat their hot flashes. However, scientists only began to understand a few of the mechanisms behind hot flashes in the early 2010s. They found that the flushing connected to low estrogen levels was primarily caused by a subset of neurons known as KNDy neurons, which produced kisspeptin, neurokinin B (NKB), and dynorphin. It was discovered in later research that hot flashes could be safely decreased by blocking the activity of certain receptors on these cells. Additionally, the first medication to treat hot flashes by blocking one of these receptors, NK3, was approved by the Food and Drug Administration in May 2023: Astellas Pharma’s fezolinetant.
Scientists had hoped that Bayer’s elinzanetant, with its dual-action design of blocking both NK3 and NK1 receptors, would lessen not only hot flashes but also the sleep issues that are frequently linked to menopause. These expectations appear to have been realized in the drug’s largest Phase III trials, which were published on Thursday in the journal JAMA.
Over seven hundred women in their 40s and 50s with moderate to severe hot flashes were randomized to receive elinzanetant or a placebo in these studies. Researchers discovered that women using the once-daily medication elinzanetant had a marked decrease in hot flashes in comparison to controls across both trials. Over 80% of the women on the medication experienced a more than 50% reduction in symptoms by the end of the studies, which took place 26 weeks later. Among them were women who had started the medication 12 weeks earlier. In addition, the participants’ quality of life related to menopause increased more than that of women taking a placebo, and they also reported less sleep disturbances. When compared to a placebo, the most frequent side effects reported by elinizanetant users were fatigue and headaches, suggesting that the medication was safe.
Elinzanetant “may offer a safe, effective, and nonhormonal treatment option to address the unmet health needs of many menopausal individuals experiencing moderate to severe [hot flashes],” according to the researchers who published the study in the Journal of Medicine.
Results from the company’s other Phase III trial of elinzanetant, which was revealed earlier in March, are similarly encouraging. Additionally, the business intends to provide regulators with information from all three trials in an effort to get the drug approved as a treatment for moderate to severe hot flashes—an approval that, barring any major surprises, should be certain.
