TOKYO, March 13, 2023 – Astellas Pharma Inc. (TSE: 4503, President and CEO: Kenji Yasukawa, Ph.D., “Astellas”) today announced The Lancet published detailed results from the pivotal Phase 3 SKYLIGHT 1™ study of fezolinetant, an investigational oral, nonhormonal compound being studied for the treatment of moderate to severe vasomotor symptoms (VMS) due to menopause. The study data was first published online March 13 in The Lancet.1 VMS, characterized by hot flashes and/or night sweats, are common symptoms of menopause.2,3
The study met the four coprimary efficacy endpoints. Fezolinetant 30 and 45 mg once daily demonstrated statistically significant improvements from baseline in VMS frequency and severity at 4 and 12 weeks compared to placebo. These improvements were observed as early as week 1, and the effects were maintained throughout the remainder of the 52-week study period. During the double-blind period, treatment-emergent adverse events (TEAEs) occurred in 37% of fezolinetant 30 mg, 43% of 45 mg and 45% of placebo participants. The safety profile of fezolinetant observed during the 40-week extension period was consistent with that of the 12-week placebo-controlled period. Over the 52 weeks of the study, the most commonly reported TEAEs were headache and COVID-19. SKYLIGHT 1 12-week topline efficacy and safety results were first presented at the American College of Obstetricians and Gynecologists 2022 Annual Meeting.
“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, M.D., Ph.D., Chair, 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.”
The key secondary endpoint was 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. While improvements in sleep disturbance were observed, statistical significance was not met for either fezolinetant dose at 12 weeks. Additional sleep analyses using 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 showed a higher proportion of patients in the fezolinetant 30 and 45 mg groups reported improvements at 4 and 12 weeks compared with placebo. Further evidence of the efficacy of fezolinetant was shown in the analyses of the Menopause-Specific Quality of Life (MENQOL) questionnaire, which demonstrated a significant and clinically meaningful4,5 improvement at 4 and 12 weeks that was maintained through 52 weeks.
“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, M.D., M.P.H., Senior Vice President and Head of Development Therapeutic Areas, 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 addition to this publication, results from SKYLIGHT 2 and SKYLIGHT 4 have recently been published in The Journal of Clinical Endocrinology & Metabolism and Obstetrics & Gynecology, respectively.6,7
Fezolinetant is an investigational selective neurokinin 3 (NK3) receptor antagonist and is not approved for use anywhere in the world. Regulatory applications for fezolinetant are under review in the U.S., EU, Switzerland and Australia. If approved, fezolinetant would be a first-in-class, nonhormonal treatment option to reduce the frequency and severity of moderate to severe VMS due to menopause.
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