The scoop on that new non-hormonal drug for hot flashes

The first non-hormonal drug to treat hot flashes – brand name Veozah, aka fezolinetant – is hitting the market. 

Part of a class of drugs known as NK3R antagonists, the drug was acquired by Japan’s Astellas Pharma and put through the required clinical trial process to determine safety and efficacy. The drugmaker made history with the first menopause commercial to screen at the Super Bowl (during the January 2023 pre-game) as part of their “What’s VMS?” campaign. 

How does it work? 

Scientists are still figuring hot flashes out, but they do know that autopsies on postmenopausal women have shown changes in the KNDy neural complex, referring to the three molecules – kisspeptin, neurokinin and dynorphin – located inside a collection of nerve cells in the hypothalamus. The working theory is that the KNDy neurons become hyperactivated, perhaps as estrogen drops and causes them to enlarge, and trigger hot flashes in the brain’s nearby thermoregulatory center. Like other NK3R antagonists, fezolinetant works to block receptors that trigger them.

How effective is it?

Veozah comes in a 45mg daily dose, supported by the results of three Phase 3 clinical trials on efficacy and a fourth on safety on women in the US, Canada and Europe. While it isn’t eliminating hot flashes, according to trial results, it is reducing them by up to 50 percent after 12 weeks. However, in another clinical trial the company announced in March 2022, in a 12-week study on 302 women in China, Taiwan and Korea, fezolinetant failed to beat the placebo. The Institute for Clinical and Economic Review, a US medicines effectiveness watchdog, has released a final evidence report “finding that the evidence is not yet adequate to demonstrate a net health benefit to the drug when compared to no pharmacological treatment”. Dr David Rind, the III trials need to be peer-reviewed and published. 

Who is it for?

NK3R antagonists could be welcome for people who can’t take menopause hormone therapy or choose not to after weighing their personal risk profile. In the US alone there are 246,000 new cases of new breast cancer a year, according to the CDC. Plus all the other people who had it, and all the other women who can’t take hormone therapy for a variety of other reasons, including a history of blood clots, high blood pressure, risk of stroke or because they can’t tolerate it. Dr Nanette Santoro, a University of Colorado professor of obstetrics and gynecology, is on the board of review for Astellas and has written several research papers on fezolinetant. She sees the drug as a good option for women who can’t take hormone therapy and also those who have “timed out” on their hormone therapy and are approaching greater risks but still having symptoms. 

Is it safe?

Dr Santoro was reassuring when she spoke about the drug to the Hot Flashes and Cool Topics podcast. “We’re not up to tens of thousands, and that’s when you can pick up anything that might be unusual or rare that might lead to further precautions or contraindications,” she said. “But as of now we have a good one year of safety on women, and it looks quite safe.” Dr Annice Mukherjee, a British endocrinologist and author of The Complete Guide to Menopause, cautioned that liver functioning should be monitored but that fezolinetant seems to be low in risks and side effects. 

“It does not impact on estrogen levels and so appears to be safe for many women in whom HRT is contraindicated or causes side effects,” she said. 

Why is it controversial?

Proponents of menopause hormone therapy seem worried that women will turn to Veozah instead, missing the chance to replace hormones for better health, longevity and disease prevention – claims that hold some basis in scientific evidence, but are also frequently exaggerated. The “What’s VMS” Super Bowl ad was cheered by some for being a watershed moment, but others disliked the “Big Pharma goes to the game” aspect. Dr Angela DeRosa, an integrative physician with three practices in Arizona, believes that having a drug just for hot flashes perpetuates the notion that menopause is just about a few symptoms. She dislikes that the drug ignores the health risks and chronic disease states that can arise out of menopause, along with this concern: “Once again they’re giving us a drug that’s a brain-altering medication to treat a specific or a couple of specific symptoms of menopause. They’re not addressing the whole patient.”

Are there other versions on the horizon?

Astellas is the strong frontrunner in the race to bring this class of drugs to market in a very competitive race. Acer Therapeutics, Bayer-acquired UK company KaNDy Therapeutics and AstraZeneca have all been working on a drug. It’s a huge potential market, too: It’s a huge potential market, too: a Jefferies report put the annual potential value at up to US $2.3 billion, and Astellas puts it at $3.7 billion.