The trial’s primary endpoint was to assess endometrial health, with additional goals of evaluating the safety and tolerability of the drug.
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Women experiencing menopause may have some relief on the horizon, according to Phase III clinical data reported Monday by Astellas Pharma. The study investigated the safety and tolerability of fezolinetant, a drug designed to help treat hot flashes and night sweats. If approved by the U.S. Food and Drug Administration, this would be a first-in-class non-hormonal option.
Between 60 and 80% of women who go through menopause experience severe vasomotor symptoms (VMS), which include hot flashes and night sweats. Currently, a common form of treatment for vasomotor symptoms is hormone therapy. However, this carries significant risks. The FDA warns that in some women, menopause hormone therapy may increase the risk of blood clots, heart attacks, strokes and breast cancer.
Astellas is trying to change that narrative by developing fezolinetant, an oral, nonhormonal selective neurokinin-3 receptor agonist. The drug works by blocking neurokinin B from binding on the kisspeptin/neurokinin/dynorphin neuron, which regulates the brain’s thermoregulatory center. Researchers at Astellas hoped that by blocking this binding, the brain’s hypothalamus could moderate hot flashes more effectively.
Fezolinetant was tested in SKYLIGHT 4, a Phase III clinical trial that was randomized, placebo-controlled and double-blind. The trial involved more than 1,800 women who were experiencing VMS symptoms in menopause in a year-long study across more than 180 sites in the U.S., Canada and Europe.
The trial’s primary endpoint was to assess endometrial health, with additional goals of evaluating the safety and tolerability of the drug. The results met the primary endpoint and supported the long-term safety and tolerability of fezolinetant. The most common adverse effects were headaches and COVID-19, which were also consistent with the placebo group.
“Vasomotor symptoms are often reported as the most bothersome symptoms of menopause, yet there has been very little innovation in this therapeutic area. I am excited by the potential of a new nonhormonal treatment option for women experiencing moderate to severe VMS associated with menopause,” said Genevieve Neal-Perry, M.D., Ph.D., chair at the UNC School of Medicine Department of Obstetrics and Gynecology.
But Astellas has competition in the women’s health market. Bayer is also leading a series of Phase III clinical development trials in its OASIS program, which is investigating the drug elinzanetant to treat VMS symptoms during menopause. Like fezolinetant , this drug is also nonhormonal, so it will be a race for regulatory approvals to see which company can market its drug first.
Other companies are also investing in menopausal or post-menopausal women’s health. In February 2022, Duchesnay, a pharmaceutical company specializing in women’s health, announced that its drug, Osphena®, was approved by Health Canada as an effective treatment for dyspareunia (painful sexual intercourse) and vaginal dryness in postmenopausal women. Osphena has already been in the U.S. for several years and has been “commercially successful and well-received,” said Dany Hallé, vice president of commercial affairs at Duchesnay.
Dyspareunia was also the target of Imvexxy, estradiol vaginal inserts created by TherapeuticsMD. These inserts deliver doses of either 4 mcg or 10 mcg of vaginal estradiol to help treat vaginal pain due to menopause.
Switzerland-based ObsEva is another pharmaceutical company developing therapies for menopause symptoms. ObsEva recently announced a partnership with Theramex to commercialize linzagolix, a best-in-class GnRH receptor agonist that helps treat uterine fibroids.
These treatments are part of worldwide investment in women’s health, a market expected to hit $27.54 billion USD by 2028.
