Experimental drug stops hot flashes without hormones

A new era of menopause treatment appears to be on the horizon. This week, pharmaceutical giant Bayer released the results of two successful Phase III trials testing its experimental drug elinzanetant for the treatment of hot flushes. The drug is now on track to become the first non-hormonal drug of its kind to be approved worldwide.

Hot flashes and night sweats are common symptoms of menopause, affecting about 80% of women at some point in their lives. Hot flashes, also known as vasomotor symptoms, are characterized by sudden feelings of warmth, flushing, and sweating, typically on the face, neck, and chest (night sweats are similar, but occur at night and during sleep). These episodes can be very uncomfortable, and in more severe cases, there is a risk of sleep disturbances and depression. Although hot flashes subside over time, they often last at least two years, and some women experience them for 10 years or more, according to the Mayo Clinic.

In the past, hot flashes have been successfully treated with hormone therapies designed to balance the declining estrogen and progesterone levels that come with menopause. However, beginning in the late 1990s, large-scale studies began to show that hormone therapies in menopausal women might increase the risk of other health problems, such as heart disease, breast cancer, and stroke—findings that soon led to a sharp and sustained decline in treatment. Later studies and more recent analyses of the data have found that these risks may have been exaggerated and can be safely mitigated. Organizations such as the North American Menopause Society currently state that the benefits of hormone treatment for hot flashes outweigh the potential harms for most women who begin therapy before age 60 and/or within ten years of their last period. However, hormone therapies remain much less popular than they once were, and there are women who are at higher risk for complications, such as women with a history of breast cancer.

Women who don't want to or can't take hormones for their hot flashes have previously had limited other options, such as low doses of certain SSRIs. But in the early 2010s, scientists finally began to unravel some of the mechanisms underlying hot flashes. They discovered that a group of neurons producing kisspeptin, neurokinin B (NKB), and dynorphin (known as KNDy neurons) were critically responsible for the hot flashes associated with low estrogen levels. 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 to treat hot flashes by blocking one of these receptors, NK3.

Bayer's elinzanetant blocks both NK3 and NK1 receptors. Scientists hope that this dual mechanism of action will not only reduce hot flashes but also the sleep problems that often accompany menopause. In the largest Phase III trials of the drug, published Thursday in the journal JAMAThese hopes seem to have been confirmed.

The trials involved over 700 women in their 40s and 50s who were diagnosed with moderate to severe hot flashes. They were randomly assigned to receive elinzanetant or a placebo. In both trials, researchers found that women who took elinzanetant (a once-daily pill) experienced a significant reduction in hot flashes compared with control subjects. At the end of the trials, 26 weeks later, over 80% of women taking the drug had seen a greater than 50% reduction in symptoms, including women who switched to the drug 12 weeks after the trial began. Participants also reported fewer sleep disturbances than women taking a placebo, and they reported greater increases in their menopause-related quality of life. Elinzanetant also appeared to be safe. The most common side effects (compared to placebo) among women taking the drug were headache and fatigue.

“Elinzanetant has the potential to provide a well-tolerated and effective non-hormonal treatment option to address the unmet health needs of many menopausal individuals with moderate to severe [hot flashes]”, say the researchers of the JAMA paper wrote.

The results follow equally promising results from the company's other Phase III trial of elinzanetant, announced in early March. And the company now plans to submit data from all three studies to regulators to secure approval of the drug to treat moderate to severe hot flashes – an approval that, barring any major surprises, should be in the bag.

As important as the introduction of these drugs is, there is still the thorny question of cost. Fezolinetant's current list price is about $550 per month, and according to Forbes, it has limited coverage by health insurers so far. These drugs may eventually become widely covered, especially as more of them come to market, but for now there is a chance that many eligible patients will not be able to afford them.