Newly published data from a phase 3 study demonstrate the safety and efficacy of fezolinetant (Astellas) for treatment of VMS due to menopause.
Astellas Pharma has announced positive data from its phase 3 SKYLIGHT 1 (NCT04003155) study of fezolinetant, which was recently published in The Lancet.1
Fezolinetant is an investigational oral, nonhormonal, selective neurokinin-3 (NK3) receptor antagonist currently being studied as a potential treatment for moderate to severe vasomotor symptoms (VMS) due to menopause.
"This publication of the SKYLIGHT 1 study is another important report of a phase 3 randomized trial assessing the utility of an investigational nonhormonal agent, fezolinetant, that targets the neurokinin 3 receptor to reduce the frequency and severity of moderate to severe VMS due to menopause, and we are honored to see it published in The Lancet," said Ahsan Arozullah, MD, MPH, senior vice president and head of development therapeutic areas at Astellas. "This manuscript, which provides further insights into the safety and effectiveness of fezolinetant, reinforces Astellas' commitment to turning innovative science into value for patients."
In the study, fezolinetant met the 4 coprimary endpoints, with both the 30 mg and 45 mg doses achieving a statistically significant improvement from baseline in VMS frequency and severity at 4 and 12 weeks vs placebo. Additionally, investigators observed these improvements as early as week 1 and were maintained throughout the 52-week study period.
"The SKYLIGHT 1 study showed that women receiving fezolinetant experienced a reduction in the frequency and severity of VMS and improvements in quality of life over the one-year treatment period," said Genevieve Neal-Perry, MD, PhD, chair of the UNC School of Medicine Department of Obstetrics and Gynecology. "As a healthcare provider, I truly understand the burden of VMS due to menopause on my own patients, and I'm really excited about this potential new nonhormonal treatment option to help women experiencing moderate to severe VMS."
Treatment-emergent adverse events (TEAEs) were also observed during the study, occurring in 37% of fezolinetant 30 mg, 43% of 45 mg, and 45% of placebo participants. The safety profile during the 40-week extension period was also consistent with the safety profile of the 12-week study period, with the more commonly reported TEAEs being COVID-19 and headache.
The secondary endpoint of the study was a mean change in the Patient-Reported Outcomes Measurement Information System Sleep Disturbance–Short Form 8b (PROMIS SD SF 8b) Total Score from baseline to 12 weeks. Improvements in sleep disturbance were observed, however, a statistical significance for either fezolinetant 30 mg or 45 mg was not met at 12 weeks. Investigators also observed further sleep analyses by utilizing the Patient Global Impression of Change in Sleep Disturbance (PGI-C SD) and Patient Global Impression of Severity in Sleep Disturbance (PGI-S SD) scales, which demonstrated a higher proportion of patients in the fezolinetant groups who reported improvements at 4 and 12 weeks vs placebo.
Also, in the analyses of the Menopause-Specific Quality of Life (MENQOL) questionnaire, fezolinetant showed a significant and clinically meaningful improvement at 4 and 12 weeks, and was maintained through 52 weeks, according to the study results.
Currently, the New Drug Application for fezolinetant is under FDA review, with a target action date of May 22, 2023.2
1. Results from Astellas' pivotal phase 3 SKYLIGHT 1 study of fezolinetant for vasomotor symptoms due to menopause published in The Lancet. Astellas Pharma. March 13, 2023. Accessed March 14, 2023. https://newsroom.astellas.us/2023-03-13-Results-from-Astellas-Pivotal-Phase-3-SKYLIGHT-1-TM-Study-of-Fezolinetant-for-Vasomotor-Symptoms-Due-to-Menopause-Published-in-The-Lancet
2. Astellas provides update on fezolinetant new drug application in US. Astellas Pharma. February 20, 2023. Accessed March 14, 2023. https://www.astellas.com/en/news/27281