SKYLIGHT trials confirm safety and efficacy of fezolinetant against sleep disturbances

SKYLIGHT trials confirm safety and efficacy of fezolinetant against sleep disturbances | Image Credit: © stokkete - © Jstokkete - stock.adobe.com.

In 2 recent phase 3 studies presented at the 2024 Annual Meeting of The Menopause Society, patient-reported sleep disturbances and impairments were improved among patients using fezolinetant to reduce vasomotor symptoms (VMS).¹

Fezolinetant is a nonhormonal, selective neurokinin 3 receptor antagonist used to reduce VMS caused by menopause. Investigators conducted a post hoc analysis to evaluate sleep disturbances and impairments in women with or without sleep disturbances at baseline.

The SKYLIGHT 1 (NCT04003155) and 2 (NCT04003142) trials included women aged 40 to 65 years with moderate-to-severe VMS caused by menopause. These participants were randomized to receive fezolinetant 30 mg, 45 mg, or placebo.

Treatment lasted for a double-blind period of 12 weeks. At the end of the 12-week period, participants entered a 40-week period where those receiving fezolinetant continued their initial dose while those taking placebo were randomized to receive fezolinetant 30 mg or 45 mg.

Outcome measures included the change in Patient-Reported Outcomes Measurement Information System Sleep Disturbance – Short Form 8b (PROMIS SD SF 8b) scores from baseline to week 12 and PROMIS Sleep-Related Impairment – Short Form 8a (PROMIS SRI SF 8a) scores from baseline to each visit. A PROMIS SD SF 8b of 55 or more at baseline indicated sleep disturbances.

Changes from baseline to weeks 12 and 52 were measured in all assessments. A mixed model repeated measures approach was used to generate 95% confidence intervals.

There were 1022 women included in the analysis, 648 of whom reported sleep disturbances at baseline while 372 did not and 2 had missing sleep disturbance data. Respondents with sleep disturbances at baseline reported more significant improvement during the trial period.

Both doses of fezolinetant led to significantly improved sleep disturbances and impairment at week 12 when compared to placebo among both women with and without sleep disturbance at baseline. The rate of fezolinetant use was also greater than placebo use at week 12, and the reported improvements remained by week 52.

These results indicated significantly improved patient-reported sleep disturbances and impairments among women with and without sleep disturbance at baseline receiving fezolinetant. Investigators concluded findings from the SKYLINE 1 and 2 trials may be applied to a wider population of menopausal women seeking VMS treatment.

This data supports the findings of the phase 3b DAYLIGHT (NCT05033886) clinical trial evaluating the safety and efficacy of fezolinetant against VMS.² The DAYLIGHT study included 450 women across 69 different sites in Turkey, Canada, and Europe.

The reduction in moderate-to-severe VMS over a 25-week period was compared among patients receiving fezolinetant 45 mg vs placebo. This endpoint was successfully reached in the fezolinetant group, and positive safety data was also reported.

Treatment-emergent adverse events (TEAEs) were reported in under 5% of patients, with common TEAEs including headache and COVID-19. Manufacturers have advised against fezolinetant use among patients with a severe kidney condition or kidney failure, cirrhosis, or taking CYP1A2 inhibitors.

Additional adverse events of fezolinetant include back pain, insomnia, diarrhea, and hot flashes. Potential severe side effects include liver problems which may present through nausea, vomiting, jaundice, and abdomen pain.

References

1. Shapiro M, Stute P, Morga A. Effect of fezolinetant on sleep disturbance and impairment in women with and without sleep disturbance at baseline: data from two phase 3 studies. Presented at the 2024 Annual Meeting of The Menopause Society. Chicago, Illinois. September 10-14, 2024.
2. Krewson C. Phase 3b study: Fezolinetant safe, effective for vasomotor symptoms. June 28, 2023. Accessed September 13, 2024. https://www.contemporaryobgyn.net/view/phase-3b-study-fezolinetant-safe-effective-for-vasomotor-symptoms