New data from the SKYLIGHT 2 trial demonstrate the reductions in frequency and severity of vasomotor menopausal symptoms in midlife women associated with the use of fezolinetant as well as potential improvements in sleep associated with use of the neurokinin-3 receptor antagonist from Astellas Pharma.
New data from a phase 3 trial suggest use of fezolinetant was associated with a significant reduction in frequency and severity of moderate-to-severe vasomotor symptoms associated with menopause.
Presented at the Endocrine Society’s annual meeting (ENDO 2022), results of the SKYLIGHT 2 trial and its extension trial demonstrate use of once-daily doses of fezolinetant in 30 or 45 mg doses provided significant reductions in severity and frequency of vasomotor menopausal symptoms and also reduced the incidence of sleep disturbances compared to placebo therapy in more than 480 women aged 40-65 years.
“VMS associated with menopause, which are characterized by hot flashes and/or night sweats, affect millions of women worldwide and can impact daily activities and quality of life,” said Genevieve Neal-Perry, MD, PhD, Distinguished Professor and Chair of Obstetrics and Gynecology at the University of North Carolina School of Medicine, in a statement.
With the agent showing promise in previous trial, SKYLIGHT 2 was launched with the intent of assessing the safety and efficacy of the neurokinin-3 receptor antagonist, fezolinetant, for reducing frequency and severity of moderate-to-severe vasomotor symptoms and sleep disturbance. A randomized, placebo-controlled, double-blind phase 3 trail, the SKYLIGHT 2 trial enrolled 501 women aged 40-65 years who were randomized to placebo therapy or 1 of 2 fezolinetant doses for the first 12 weeks followed by 40-week active treatment extension period where patients randomized to placebo were switched to fezolinetant.
Efficacy outcomes of interest were change through 12 weeks in vasomotor menopausal symptom frequency, vasomotor menopausal symptom severity, and Patient-reported Outcomes Measurement Information System Sleep Disturbance– Short Form 8b (PROMIS) Total Score. Persistence of efficacy for fezolinetant was assessed without statistical comparators during the extension period.
Overall, 484 women were included in the present analysis, with 166 patients receiving fezolinetant 30 mg and 167 receiving fezolinetant 45 mg for the entire duration of the trial. A group of 76 were originally randomized to placebo therapy and switched to fezolinetant 30 mg for the extension trial while 75 were randomized to placebo and switched to fezolinetant 45 mg for the extension trial.
Upon analysis, investigators observed in improvements in vasomotor menopausal symptoms frequency and severity through week 12, which were maintained throughout the duration of the 52-week trial. Investigators also pointed out use of fezolinetant provided reductions in frequency and severity became greater beyond the 12-week mark of the trial. From baseline to week 12, there were least squares mean reductions of –6.83 (SE, 0.39) symptoms per day for fezolinetant 30 mg and –7.50 (SE, 0.39) for fezolinetant 45 mg. From baseline to week 52, there were least squares mean reductions of symptoms per day of –8.03 (SD, 4.53) for fezolinetant 30 mg and –8.48 (SD, 3.98) for fezolinetant 45 mg.
When assessing symptom severity, the least squares mean reductions from baseline to week 12 were –0.64 (SE, 0.06) for fezolinetant 30mg and –0.77 (SE, 0.06) for fezolinetant 45mg. From baseline to week 52, the least squares mean reductions were –0.83 (SD, 0.82) for fezolinetant 30 mg and –0.95 (SD, 0.78) for fezolinetant 45 mg. Investigators pointed out women who were rerandomized to fezolinetant after the first 12 weeks experienced a reduction in frequency and severity of vasomotor menopausal symptoms were consistent with those seen in women receiving fezolinetant throughout the duration of the trial.
When assessing changes in sleep disturbances, results suggested fezolinetant was associated with reduction in PROMIS Total Scores. From baseline to week 12, the least squares mean reduction observed with fezolinetant 30 mg were -4.1 (SE, 0.5) and -5.5 (SE, 0.5) with fezolinetant 45 mg. From baseline to week 52, the least squares mean reduction was -6.3 (SD, 7.3) for fezolinetant 30 mg and -5.7 (SD, 7.9) for fezolinetant 45 mg. Investigators noted the safety profile observed during the 40-week extension period was consistent with the safety profile from the 12-week placebo-controlled period.
“These results, along with other fezolinetant studies, will be important in understanding the use of this oral nonhormonal selective NK3 receptor antagonist to treat moderate-to-severe VMS associated with menopause,” Neal-Perry said.
This study, “Fezolinetant for Treatment of Moderate-to-severe Vasomotor Symptoms Associated with Menopause: Results from a 52-week Study (Skylight 2),” was presented at ENDO 2022.