Fezolinetant reduces hot flashes associated with menopause in diverse population

Key takeaways :

• Fezolinetant is a nonhormonal neurokinin 3 receptor antagonist approved by the FDA to treat moderate to severe hot flashes.
• New analysis shows fezolinetant was efficacious in diverse subgroups.

BALTIMORE — Treatment with once-daily oral fezolinetant was effective for reducing moderate to severe hot flashes associated with menopause in a diverse population, according to findings reported at the ACOG Annual Clinical & Scientific Meeting.

This included those with a greater burden of severe and frequent vasomotor symptoms, Black women, women with an elevated BMI and current smokers.

As Healio previously reported, the FDA announced on May 12 it approved fezolinetant (Veozah, Astellas Pharma) for the treatment of moderate to severe hot flashes due to menopause. Approval was based on results of two phase 3 trials, SKYLIGHT 1 and 2, that included women aged 40 to 65 years with moderate to severe vasomotor symptoms, defined as seven or more events in 24 hours.

A new analysis, results of which were presented at the ACOG Annual Clinical & Scientific Meeting, looked at the relationship between individual-related (intrinsic) and outside-influence (extrinsic) factors and the efficacy of fezolinetant from baseline to week 12.

Genevieve Neal-Perry, MD, PhD

“This analysis aimed to understand whether we are meeting the needs of those who are at increased risk, or those who we know tend to have more severe and more frequent hot flashes — for example, African American women and those with an elevated BMI. Their burden is higher,” Genevieve Neal-Perry, MD, PhD, Robert A. Ross Distinguished Professor and chair of obstetrics and gynecology at the University of North Carolina School of Medicine, told Healio during the ACOG meeting. “The new data showed that the frequency of hot flashes was improved in all of these groups. We also saw similar reductions in the severity of hot flashes; for those who did continue to have hot flashes, the severity was reduced too."

Overall, 1,122 participants took one or more doses of fezolinetant for up to 52 weeks. Researchers reported consistent improvements in the frequency of vasomotor symptoms with fezolinetant 45 mg compared with placebo across subgroups, including age younger than 55 years (least square mean difference, –2.78) or older than 55 years (–2.24), white race (–2.17), Black race (–3.67), BMI of 30 kg/m² or higher (–2.87), current smokers (–3.48), former or never smokers (–2.32), those living in Europe (–1.5) and those living in North America (–2.95).

The researchers reported similar trends in efficacy with the 30 mg dose.

Fezolinetant is a first-in-class neurokinin 3 receptor antagonist approved by the FDA for treatment of moderate to severe vasomotor symptoms. This medication is not a hormone;it binds and blocks activities of the neurokinin 3 receptor with a high afficity, which impacts the region of the brain that regulates body temperature and triggers hot flashes.

“Before Veozah, treatments options were not selective for the neurons that trigger hot flashes because we didn’t understand the biology of hot flashes. Veozah was developed specifically to selectively manage the neuroendocrine source of hot flashes,” Neal-Perry said in an interview.

“For far too long, people with hot flashes have suffered. We now have available highly selective and effective nonhormonal therapy in our armamentarium to treat hot flashes and we have an opportunity to improve the quality of life of those affected. It is fabulous to know that people affected with hot flashes have great nonhormonal options.,” Neal-Perry told Healio.

Reference:

• Santoro N, et al. Obstet Gynecol. 2023;doi:10.1097/01.AOG.0000929848.45312.e5.