Elinzanetant

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.

iStock, SiberianArt After a leading study caused the FDA to slap its most stringent warning on hormone replacement therapies for menopause more than two decades ago, the regulator is changing course in what FDA Commissioner Marty Makary called a “historic day for women in the United States.” The FDA will remove the black box warning on all hormone replacement therapies, reversing a 22-year-old decision Health Secretary Robert F. Kennedy Jr. characterized in a press conference Monday morning as the American medical establishment “turn[ing] its back on women.” “Millions of women were told to fear the very therapy that could have given them strength, peace and dignity through one of life’s most difficult transitions, menopause,” Kennedy said, standing alongside FDA Commissioner Marty Makary, Second Lady Usha Vance and other government representatives and physicians. “That ends today.” The black box warning—the strongest the FDA can levy on a product—for hormone replacement therapies (HRT) stemmed from a 2002 landmark study called the Women’s Health Initiative (WHI) that found an increased risk of heart disease and breast cancer associated with the class of drugs. In a statement Monday, the Department of Health and Human Services noted that this increase was “statistically non-significant” and pointed out that the average age of its participants was 63 years, “over a decade past the average age of a woman experiencing menopause,” according to the agency. The global HRT market was estimated to be nearly $24 billion in 2024 and is projected to reach nearly $40 billion by 2033, with North America accounting for the largest share and Asia Pacific the fastest growing market, according to Grand View Research . Leading pharma players are Bayer, Pfizer, Ascendis Pharma and Novartis Gene Therapies. The FDA’s decision follows the convening of an expert panel on menopause and hormone replacement therapy in July. This represents a new format for the agency during which an “independent panel of scientific experts” will “review the latest scientific evidence, evaluate potential health risks, explore safer alternatives” and possibly offer recommendations for regulatory action. The panel faced criticism over apparent bias, with Diana Zuckerman, president of the nonprofit National Center for Health Research, telling BioSpace in September that she was struck by the lack of nuance presented during the session, as well as a later panel focused on SSRI use during pregnancy. During Monday’s press conference, Kennedy listed a number of statistics, including that HRT has been found to reduce the risk of cardiovascular disease and mortality by as much as 50%, Alzheimer’s disease by 35% and bone fractures by 50–60%. Kennedy claimed these factors combined could “extend [women’s] lives by as much as 10 years.” Makary, who called Monday a “historic day for women in the United States,” added that women who took estrogen alone in fact had a 24% reduction in breast cancer. A breast cancer research page attributing this stat to the WHI notes a 23% reduction in breast cancer diagnoses and adds that women taking estrogen-only HRT are 44% less likely to die from the disease. Prior to 2002, one in four American women used hormone replacement therapy, Kennedy claimed. Today, he said, that number is fewer than one in 20. “That’s not progress, that’s neglect, that’s malpractice. We can no longer accept a culture of fear that blocks innovation and keeps patients from proven therapies.” In related news, the FDA recently signed off on Bayer’s oral therapy Lynkuet for moderate to severe hot flashes in menopausal women. Lynkuet is the first FDA-approved therapy that blocks both the neurokinin 1 and neurokinin 3 receptors to treat this common symptom of menopause.