Fezolinetant safe and effective treatment for VMS associated with menopause: Phase 3 SKYLIGHT trial

USA: According to data presented at the NAMS Annual Meeting, women using fezolinetant for moderate to severe vasomotor symptoms experienced a reduction in symptom severity and sleep disturbances.

The Phase 3 SKYLIGHT trial showed the 52-week safety and tolerability of fezolinetant 30 mg and 45 mg once daily for treating moderate to severe vasomotor symptoms (VMS) associated with menopause. Stellas Pharma Inc. had presented the trial results, which was presented at The North American Menopause Society Annual Meeting.

The study evaluated the safety and tolerability of fezolinetant, an investigational oral, nonhormonal compound being studied to treat moderate to severe vasomotor symptoms (VMS) associated with menopause. VMS, characterized by hot flashes and/or night sweats, are common symptoms of menopause.

SKYLIGHT 4 results demonstrate the 52-week safety and tolerability of fezolinetant 30 mg and 45 mg once daily. Safety analyses demonstrated that both endometrial hyperplasia and endometrial malignancy were within pre-specified limits for fezolinetant-treated patients; reported treatment-emergent adverse events (TEAEs) were generally mild or moderate in severity; and headache and COVID-19 were the most common TEAEs, with similar incidences for fezolinetant and placebo.

The frequency of elevated liver enzymes was low across groups, and elevations were generally asymptomatic, isolated, transient and resolved on treatment or soon after study drug discontinuation.

"There is an unmet need for safe and effective nonhormonal treatment options for VMS associated with menopause, which can adversely impact daily quality of life," said Genevieve Neal-Perry, M.D., Ph.D., Chair, UNC School of Medicine Department of Obstetrics and Gynecology. "The SKYLIGHT 4 study results demonstrate the long-term safety and tolerability of fezolinetant, providing further support for its potential use as a treatment for VMS."

In addition, pooled efficacy data from SKYLIGHT 1™ and SKYLIGHT 2™ evaluating early response to fezolinetant, its impact on sleep and treatment response analyzed by race will be presented.

"Results of the SKYLIGHT 4 study and the pooled analyses from the SKYLIGHT 1 and 2 studies provide further insights into the safety and effectiveness of fezolinetant," said Ahsan Arozullah, M.D., M.P.H., Senior Vice President and Head of Development Therapeutic Areas, Astellas. "Through our clinical development program, we are excited to further characterize the clinical profile of fezolinetant for women who experience hot flashes as part of menopause."

Fezolinetant is an investigational selective neurokinin 3 (NK3) receptor antagonist and is not approved for use anywhere in the world. New Drug and Marketing Authorization applications for fezolinetant are under review in the U.S. and Europe, respectively. If approved, fezolinetant would be a first-in-class, nonhormonal treatment option to reduce the frequency and severity of moderate to severe VMS associated with menopause.

Astellas will also present three abstracts examining the association between VMS and weight gain, sleep quality and work productivity.

References: 

1 Utian WH. Psychosocial and socioeconomic burden of vasomotor symptoms in menopause: a comprehensive review. Health Qual Life Outcomes. 2005;3:47.

2 Jones RE, Lopez KH, eds. Human Reproductive Biology. 4th ed. Waltham, MA: Elsevier, 2014:120.

3 Makara-Studzinska MT, Krys-Noszczyk KM, Jakiel G. Epidemiology of the symptoms of menopause - an intercontinental review. Przegl Menopauzalny [Menopause Rev]. 2014;13:203-211.

4 Gold EB, Colvin A, Avis N, et al. Longitudinal analysis of the association between vasomotor symptoms and race/ethnicity across the menopausal transition: study of women's health across the nation. Am J Public Health. 2006;96:1226-1235.

5 Freeman EW, Sammel MD, Sanders RJ. Risk of long-term hot flashes after natural menopause: evidence from the Penn Ovarian Aging Study cohort. Menopause. 2014;21:924-932.