A new era in menopause treatment may be upon us: This week, the pharmaceutical company Bayer announced successful results from two Phase 3 trials testing the experimental drug erinzanetant to treat hot flashes, making it the first non-hormonal treatment to be approved anywhere in the world.
Hot flashes and night sweats are common symptoms of menopause, affecting approximately 80% of women over their lifetime. Formally known as vasomotor symptoms, hot flashes are characterized by sudden warmth, redness, and sweating, usually around the face, neck, and chest (night sweats are similar, but occur at night or while sleeping). These symptoms can be very uncomfortable, and when severe, they are thought to increase the risk of sleep deprivation and depression. Hot flashes lessen over time, but many last for at least two years, and some women may experience them for more than a decade, according to the Mayo Clinic.
Historically, hot flashes have been effectively treated with hormone therapy, which aims to replace the estrogen and progesterone levels that decline with menopause. However, beginning in the late 1990s, large-scale trials began to show that hormone therapy may increase the risk of other health problems, such as heart disease, breast cancer, and stroke, in menopausal women, which soon led to a significant and ongoing decline in treatment. Subsequent studies and more recent data analyses have found that these risks may have been exaggerated and can be safely mitigated. Organizations such as the North American Menopause Society now say that for most women who begin treatment under age 60 and/or within 10 years of their last menstrual period, the benefits of hormone therapy for hot flashes outweigh the potential harms. However, hormone therapy is not as popular as it once was, and some women, such as those with a history of breast cancer, are at higher risk of complications from hormone therapy.
Women who don’t want or can’t take hormone therapy for hot flashes have 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 that produce kisspeptin, neurokinin B (NKB), and dynorphin (known as KNDy neurons) are crucial in triggering the flushing associated with low estrogen levels. Subsequent studies found that inhibiting 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 fezolinnetant, the first drug to treat hot flashes by inhibiting one of these receptors, NK3.
Bayer’s erinzanetant is a dual-action design that blocks both the NK3 and NK1 receptors, which scientists hope will not only reduce hot flashes but also the sleep problems that often accompany menopause. The drug’s largest-ever Phase 3 trial, published Thursday in the journal Neurol. JAMAAnd it looks like that expectation has become a reality.
The study included more than 700 women in their 40s and 50s who were diagnosed with moderate to severe hot flashes and were randomly assigned to receive either erinzanetant or a placebo. Throughout both trials, researchers found that women who took erinzanetant (a tablet taken once a day) experienced a significant reduction in hot flash symptoms compared to the control group. By the end of the study after 26 weeks, more than 80% of women taking the drug experienced a 50% or greater reduction in symptoms, including women who switched to the drug 12 weeks into the study. Participants also reported fewer sleep disturbances and greater improvements in menopause-related quality of life than women taking the placebo. Erinzanetant also appeared to be safe, with headaches and fatigue being the most common adverse events in people taking the drug (compared to placebo).
“Erinzanetant has the potential to be a well-tolerated and effective non-hormonal treatment option to address the unmet health needs of many menopausal women with moderate to severe menopausal symptoms. [hot flashes]” the researchers said. JAMA I wrote the paper.
The results follow similarly encouraging results from another Phase 3 study of the company’s drug, erinzanetant, announced earlier this March. The company now plans to submit data from all three studies to regulators for approval of the drug for the treatment of moderate to severe hot flashes. Barring any major surprises, approval should be a certainty.
While the arrival of these drugs is important, there’s a troubling issue of cost. According to Forbes, the list price for fezolinethant is currently about $550 per month, and insurance coverage has been limited so far. These drugs may eventually become more widely covered, especially as more come to market, but for now they may be out of reach for many eligible patients.
