Astellas Announces Positive Phase 3 SKYLIGHT 2 Trial Results for Fezolinetant in Menopausal Moderate-to-Severe VMS

Compiled & Translated by | newborn

Astellas recently announced the 12-week results from the pivotal Phase 3 SKYLIGHT 2 clinical trial. The trial is evaluating fezolinetant for the treatment of moderate-to-severe vasomotor symptoms (VMS) associated with menopause. VMS, characterized by hot flashes and/or night sweats, are common symptoms of menopause.

Fezolinetant is a non-hormonal, selective neurokinin-3 receptor (NK3R) antagonist that blocks specific receptors in the brain's temperature control center (the hypothalamus) to reduce the frequency and severity of menopause-associated VMS.

Results from the SKYLIGHT 2 study demonstrated that once-daily oral fezolinetant at doses of 30 mg and 45 mg met the study's co-primary endpoints: statistically significant reductions in the frequency and severity of moderate-to-severe vasomotor symptoms (VMS) at Week 4 and Week 12 compared with placebo. The results also indicated that during the 12-week placebo-controlled period, improvements in both VMS frequency and severity were greater than those observed with placebo, and both doses of fezolinetant showed improvement in VMS within the first week of treatment. The specific data are presented below:

For the co-primary endpoints of reduction in mean frequency of moderate-to-severe VMS: (1) Compared with placebo, the mean daily changes for the 30 mg dose of fezolinetant at Week 4 and Week 12 were -1.82 (p<0.001) and -1.86 (p<0.001), respectively. (2) Compared with placebo, the mean daily changes in VMS frequency for the 45 mg dose of fezolinetant at Week 4 and Week 12 were -2.55 (p<0.001) and -2.53 (p<0.001), respectively.

For the co-primary endpoint of reduction in the mean severity of moderate to severe VMS: (1) compared with placebo, the mean daily change for the 30 mg dose of fezolinetant was −0.15 (p ≤ 0.021) at Week 4 and −0.16 (p = 0.049) at Week 12. (2) compared with placebo, the mean daily change for the 45 mg dose of fezolinetant was −0.29 (p ≤ 0.001) at both Week 4 and Week 12.

In this study, 40%, 36%, and 32% of patients in the 30 mg, 45 mg, and placebo groups, respectively, reported treatment-emergent adverse events (TEAEs). Headache was the most common TEAE in the fezolinetant groups, occurring in 3%, 4%, and 2% of patients in the 30 mg, 45 mg, and placebo groups, respectively. In the fezolinetant groups, serious TEAEs occurred in less than 2% of patients, and no drug-related serious TEAEs were reported. Detailed safety results will be disclosed upon completion of the fezolinetant Phase 3 program, which also includes the SKYLIGHT 1 and SKYLIGHT 4 studies.

VMS is the most common symptom for which menopausal women seek treatment, yet non-hormonal options for women and healthcare providers are limited. These results from the SKYLIGHT 2 study demonstrate that fezolinetant can help reduce the frequency and severity of moderate to severe VMS.

If the Phase III program is successful and receives marketing approval, fezolinetant is expected to provide a first-in-class, non-hormonal treatment option for moderate-to-severe vasomotor symptoms (VMS) associated with menopause.

Reference: Astellas to Present Fezolinetant 12-Week Findings from Phase 3 SKYLIGHT 2™ Trial in Oral Session at The North American Menopause Society 2021 Annual Meeting