Fezolinetant

More than two decades after the Women's Health Initiative (WHI) linked the use of hormone therapy to an increased risk for breast cancer, heart disease and stroke in postmenopausal women, the FDA is now walking back the resulting warnings it added to such treatments' labels. The US regulator said Monday that it has "re-considered the benefit/risk balance of these drugs" and is requesting the removal of boxed warnings for cardiovascular diseases, breast cancer and probable dementia from menopausal hormone therapies (MHTs) used to treat vasomotor symptoms (VMS), such as hot flashes.The WHI's findings had a major chilling effect on women seeking out hormone therapy, as well as the larger medical community's interest in menopause, Yesmean Wahdan told FirstWord in a recent interview. She serves as Bayer's senior vice president and head of medical affairs in the US and North America. But now, menopause "is having its moment… it is now at centre stage," Wahdan said. "Research is being done." For more from that interview, see ViewPoints: Inside Bayer's bet on menopause momentum, and why the health stakes are high.The FDA announcement comes a few weeks after the agency approved Bayer's Lynkuet (elinzanetant), a non-hormonal treatment for moderate-to-severe VMS. The dual neurokinin-1 and neurokinin-3 (NK-1,3) receptor antagonist is the second non-hormonal option to hit US shelves, following the 2023 clearance of Astellas' rival NK-3 antagonist Veozah (fezolinetant).However, uptake for Veozah has been hampered by post-marketing cases of elevated liver enzymes, which prompted the FDA to increase the number of blood tests to six from four during the first 12 months of treatment (see – ViewPoints: Bayer hoping elinzanetant can change the VMS narrative and Spotlight On: Astellas’ liver tox pain with Veozah could be Bayer’s gain in VMS).And Lynkuet isn't without its own drawbacks. Its label carries a warning for central nervous system effects, including dizziness and somnolence. A recent FirstWord survey of US physicians found that 66% were either somewhat (48%) or very (18%) concerned about such effects (see – Physician Views Results: Doctors warm to Bayer's Lynkuet, though side effects could cool enthusiasm).Questions and concernsIn its announcement, the FDA said that for years, it has "received questions about whether the boxed warnings… were warranted" for MHTs, adding that "certain groups have raised concerns about the applicability of the WHI studies' methodologies and interpretations."Specifically, the average participant age in the WHI was 63, about 10 years older than the average age at which women in the US begin experiencing menopause — "meaning that the age-related health conditions in the WHI population did not match the typically younger and healthier women who may start MHT for bothersome VMS," the FDA said. A separate release from the Department of Health and Human Services (HHS) also noted that WHI participants "were given a hormone formulation no longer in common use."Following a review of "the current relevant literature," including an analysis from younger cohorts in the WHI who started MHT within 10 years of menopause onset, the FDA concluded that hormone therapy was not associated with increased cancer mortality, and was, in fact, linked to a reduced risk of all-cause mortality and fractures.Given the findings, the agency is now working with drugmakers to update the labels of MHTs to remove certain warnings, though one carried by systemic oestrogen-alone products for endometrial cancer will remain in place.

The Food and Drug Administration late Friday approved a new, non-hormonal treatment for postmenopausal women who experience vasomotor symptoms, also known as hot flashes.The drug, called Lynkuet and developed by Bayer, was cleared to treat moderate severe hot flashes due to menopause. Approval was supported by three late-stage trials that enrolled thousands of women. Data showed treatment reduced both the frequency and severity of hot flashes.There is a need for more individualized approaches to menopause care, and Lynkuetaddresses a significant gap in treatment options, said Christine Roth, Bayers executive vice president of global product strategy and commercialization, in a statement.Vasomotor symptoms typically occur during and after menopause, a transition when a womans menstrual cycle stops. The drop in estrogen levels thats associated with menopauseleads to these symptoms, which range in severity and can be life-disrupting,sometimes for years.Menopause hormone therapy, also known as hormone replacement therapy, is one treatment option. However, not everyone is a good candidate for hormonal therapy, while others might opt out due to health risks.One other non-hormonal treatment is on the market for vasomotor symptoms: Astellas Pharmas Veozah. The drug was approved in 2023 but has struggledcommercially due to lower-than-expected demand and complications with reimbursement. Most recently, the FDA added a black box warningfor possible liver damage on the drugs labeling.Bayers drug works similarly to Veozah by blocking what are known as neurokinin receptors. Lynkuet targets two receptors, NK1 and NK3, which help regulate body temperature, while Veozah targets just NK3.We think that there's a benefit from targeting two receptors, said JoAnn Pinkerton, a lead investigator in a clinical trial testing Lynkuet, and a professor of obstetrics and gynecology at the University of Virginia Health System.We saw a very rapid reduction in hot flashes and night sweats similar to [Veozah], and an improvement in the severity of the hot flashes, as well as an improvement in health-related quality of life and sleep, Pinkerton said in a recent interview.The approval of Veozah and, now, Lynkuet, is spotlighting an area thats receiving heightened attention among investors and biotech companiesand greater awareness more broadly. Menopause is having a moment with all of the excitement of new therapies. And many women in the workforce are recognizing that perimenopause and menopause are having an effect on their ability to function at a high level, Pinkerton said.One example of that growing attention was an FDA panel discussion earlier this year on hormonal therapies for menopause. At that meeting, a panel that included Pinkerton called for the removal of warning labels associated with treatment.Though the FDA hasnt issued further guidance since,Pinkerton hopes the meeting, and surge in research interest, are signs of things to come.I think [the key] is that women have to support each other and try to move this field forward in this country and other countries, she said.Lynkuet is expected to be available in the U.S. in November.Wholesale acquisition cost of Lynkuet is $625 for a 30-day supply. Pricing will vary based on insurance. Bayer has also partnered with digital pharmacy BlinkRx to provide access to the drug at a lower cost. '