Real-world data link fezolinetant to fewer nighttime awakenings

Fezolinetant (Veozah) was associated with statistically significant improvements in objective and patient-reported sleep measures among women with bothersome vasomotor symptoms (VMS) in a second preliminary analysis of the ongoing OPTION-VMS study, according to Marla Shapiro, CM, MDCM, CCFP, MHSc, FRCPC, FCFP, MSCP.¹

The prospective, multicenter US study, which was presented at the International Menopause Society 20th World Congress on Menopause, enrolled women aged 40 to 75 years. As of March 2026, 993 users of nonhormonal therapy were enrolled, 859 of whom completed baseline and at least 1 postbaseline assessment. Treatments were grouped by initial prescription: fezolinetant, selective serotonin reuptake inhibitors or serotonin-norepinephrine reuptake inhibitors (SSRIs/SNRIs), and other nonhormonal therapies. Sleep was assessed objectively with a medical-grade wearable actigraphy device and subjectively with the Patient-Reported Outcomes Measurement Information System (PROMIS) Sleep Disturbance Short Form 8b at weeks 4, 8, and 12.¹ An earlier preliminary analysis had also reported sleep improvements with fezolinetant.²

At week 12, fezolinetant was associated with reductions in wakefulness after sleep onset (least squares mean change, −9.45 minutes; 95% CI, −13.93 to −4.96), sleep latency (−1.24 minutes; 95% CI, −1.81 to −0.67), and nighttime awakenings (−2.61; 95% CI, −4.07 to −1.15), as well as increased sleep efficiency (+1.95%; 95% CI, 0.93-2.97) and improved PROMIS total T-scores (−5.69; 95% CI, −6.95 to −4.44) (all P < .001). Improvements were also significant at weeks 4 and 8.¹

Apart from a low-dose SSRI approved in the United States, nonhormonal VMS treatments had historically been used off label, Shapiro noted. The other nonhormonal group consisted primarily of gabapentin, with some pregabalin and clonidine. Results were limited to within-group changes from baseline.

"The study was not designed to compare treatment groups. So they're not head-to-head comparisons," Shapiro said.

SSRIs/SNRIs were not associated with statistically significant improvements in any actigraphy end point. In the other nonhormonal group, the only significant actigraphy improvement was in wakefulness after sleep onset, at weeks 4 and 12. Patient-reported sleep improved significantly in both groups, with PROMIS scores moving from the mild to the no-disturbance range by week 4 with SSRIs/SNRIs and by week 8 with other nonhormonal therapies.¹

No new safety signals emerged. The incidence of drug-related treatment-emergent adverse events, including those leading to drug withdrawal or interruption, was very low with fezolinetant, and no drug-related serious adverse events or hepatotoxicity occurred.¹

"There were 2 cumulative cases of non-serious mild elevated LFTs, neither of which led to treatment or study discontinuation," Shapiro said. Headache and upper respiratory infection were the most commonly reported events, each at a rate of approximately 1.5%.

Findings were consistent across racially and ethnically diverse women, women older than 65 years, women in the menopause transition, and women with obesity. Together with SKYLIGHT trial data from nearly 3000 women and postapproval experience, the findings reinforced a favorable benefit-risk profile for fezolinetant.³

References

1. Shapiro M, Cano A, Nappi RE, et al. Effect of fezolinetant on sleep disturbance and impairment during treatment of vasomotor symptoms due to menopause. Maturitas. 2024;186:107999. https://doi.org/10.1016/j.maturitas.2024.107999
2. Ebert M. Fezolinetant shows significant real-world improvements in vasomotor symptoms, sleep. Contemporary OB/GYN. October 23, 2025. https://www.contemporaryobgyn.net/view/fezolinetant-shows-significant-real-world-improvements-in-vasomotor-symptoms-sleep
3. Neal-Perry G, Cano A, Lederman S, et al. Safety of fezolinetant for vasomotor symptoms associated with menopause: a randomized controlled trial. Obstet Gynecol. 2023;141(4):737-747. https://pubmed.ncbi.nlm.nih.gov/36897180/