FDA OKs Hormone-Free Pill for Hot Flashes

The FDA approved the first-in-class drug fezolinetant (Veozah) for the treatment of moderate to severe hot flashes caused by menopause, the agency announced Friday.

The oral neurokinin 3 (NK3) receptor antagonist is a non-hormonal treatment that works to block the activities of the NK3 receptor, which plays a role in the brain’s regulation of body temperature.

“Hot flashes as a result of menopause can be a serious physical burden on women and impact their quality of life,” said Janet Maynard, MD, MHS, director of the Office of Rare Diseases, Pediatrics, Urologic and Reproductive Medicine in the FDA’s Center for Drug Evaluation and Research, in a statement. “The introduction of a new molecule to treat moderate to severe menopausal hot flashes will provide an additional safe and effective treatment option for women.”

The 45-mg once-daily pill should be taken at the same time each day, with or without food, according to the drug’s label.

It’s estimated that about 80% of menopausal women experience hot flashes. The only other nonhormonal treatment option is the antidepressant paroxetine (Brisdelle), which was approved by the FDA back in 2013. Other hot flash therapies include herbal remedies and drugs used off-label, like gabapentin, clonidine, and other selective serotonin reuptake inhibitors (SSRIs).

After being granted priority review by the FDA, the new approval was based on the phase III BRIGHT SKY clinical program, which included two pivotal trials. In the second of these trials — the SKYLIGHT-2 trial — fezolinetant cut the frequency of hot flashes by an average of 7.5 per day by week 12. The benefit was sustained during a 40-week extension phase, averaging 8.48 fewer vasomotor symptoms daily. The severity of these symptoms also significantly improved while on treatment.

The 45-mg dose also resulted in improvements in sleep disturbances.

Fezolinetant “is a boon because we haven’t had other treatment options that are highly effective without significant side effects,” said SKYLIGHT-2 lead investigator Genevieve Neal-Perry, MD, PhD, of the University of North Carolina at Chapel Hill, during a press conference at ENDO 2022, the annual meeting of the Endocrine Society.

The most common side effects with fezolinetant included abdominal pain, diarrhea, insomnia, back pain, hot flashes, and elevated hepatic transaminases.

A blood test to monitor liver values is required prior to starting treatment, and should be repeated again at treatment months 3, 6, and 9. Patients should also monitor themselves for symptoms of liver damage, like nausea, vomiting, or yellowing of the skin and eyes.

Fezolinetant is contraindicated in patients with cirrhosis, severe kidney problems or kidney failure, and those taking CYP1A2 inhibitors.