Actigraphy supports fezolinetant sleep improvements by week 4

Objective sleep data captured by actigraphy in the phase 4 OPTION-VMS study corroborated patient-reported sleep improvements with fezolinetant (Veozah), according to Marla Shapiro, CM, MDCM, CCFP, MHSc, FRCPC, FCFP, MSCP, in an interview regarding a second preliminary analysis presented at the International Menopause Society 20th World Congress on Menopause.¹

Menopause significantly impaired sleep and quality of life, with disturbances beginning in perimenopause, Shapiro said. Improvements in patient-reported sleep disturbance with fezolinetant were demonstrated in the pivotal SKYLIGHT studies using the Patient-Reported Outcomes Measurement Information System Sleep Disturbance Short Form 8b (PROMIS SD SF 8b).¹ However, questionnaires were subject to recall bias, and patients who reported poor sleep often could not specify which components of sleep were affected, according to Shapiro.

OPTION-VMS (NCT06049797) was an ongoing, prospective, multicenter US study of women aged 40 to 75 years with bothersome vasomotor symptoms who were prescribed nonhormonal therapy in routine clinical practice.² Participants wore a medical-grade device that measured wakefulness after sleep onset, sleep efficiency, sleep latency, and nighttime awakenings, which were assessed alongside PROMIS SD SF 8b scores. The objective data served to validate the PROMIS SD SF 8b findings while providing considerably more detail, Shapiro said. At the March 2026 analysis, 993 nonhormonal therapy users were enrolled, and 859 had completed the Menopause-Specific Quality of Life questionnaire at baseline and at least 1 postbaseline visit.

Among patients treated with fezolinetant, actigraphy showed statistically significant improvements at week 12 (all P < .001), with mean reductions of 9.45 minutes in wakefulness after sleep onset, 1.24 minutes in sleep latency, and 2.61 nighttime awakenings, as well as a 1.95% increase in sleep efficiency. PROMIS SD SF 8b T-scores decreased by a mean of 5.69 points. Statistically significant improvements in these endpoints were also observed at weeks 4 and 8 (P < .05). Drug-related adverse events were infrequent, with 2 hepatic laboratory test abnormalities and no drug-related serious adverse events or hepatotoxicity.

Improvements were evident at week 4, the first time point assessed, with patients moving from mild sleep disturbance at baseline to no sleep disturbance, and persisted thereafter, according to Shapiro. Among the end points, she highlighted "the nighttime awakenings, which is really the hallmark of sleep disturbance in perimenopause and menopause, like that frequent awakening."

The concordance between subjective and objective improvements at the same time points was reassuring and supported the validity of PROMIS SD SF 8b data used across fezolinetant studies, Shapiro said. Total sleep time was not necessarily the parameter that changed.

"You may not see improvements in total time slept because patients will say, well, it was still from 8 to whatever time it was," Shapiro said. Rather, improvements occurred in the period between sleep onset and final awakening—details patients often could not recall the following day.

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. Fitch J. IMS: fezolinetant's improvements in sleep quality, hot flashes as early as week 4. Contemporary OB/GYN. Published October 1, 2026. https://www.contemporaryobgyn.net/view/fezolinetant-option-vms-real-world-sleep-vasomotor-symptoms-ims-2026