The Food and Drug Administration (FDA) has accepted the New Drug Application (NDA) for fezolinetant, an investigational, nonhormonal selective neurokinin-3 receptor (NK3R) antagonist for the treatment of moderate to severe vasomotor symptoms (VMS) associated with menopause.

Fezolinetant works by inhibiting neurokinin B binding on the kisspeptin/neurokinin/dynorphin neuron to regulate neuronal activity in the thermoregulatory center in the hypothalamus. The NDA is supported by the BRIGHT SKY program, which included efficacy and safety data from the pivotal phase 3 SKYLIGHT 1 (ClinicalTrials.gov: NCT04003155) and 2 (ClinicalTrials.gov: NCT04003142) studies, along with the SKYLIGHT 4 safety study (ClinicalTrials.gov: NCT04003389). 

The randomized, double-blind, placebo-controlled SKYLIGHT 1 and 2 studies evaluated the efficacy and safety of fezolinetant 30mg and 45mg orally once daily in 1028 women aged 40 to 65 years with moderate to severe VMS. The first 12 weeks of the trials were double-blinded and placebo-controlled, and were followed by 40-week active treatment extension periods.

Findings from both trials showed that both doses of fezolinetant met all 4 co-primary end points achieving statistically significant reductions in the frequency and severity of moderate to severe VMS at week 4 and week 12 from baseline compared with placebo. The most common treatment emergent adverse event for fezolinetant was headache. The incidence of serious TEAEs was reported to be less than 2% in patients treated with fezolinetant.

A Prescription Drug User Fee Act target action date of February 22, 2023 has been set for this application.

“The FDA’s acceptance of our NDA for fezolinetant brings us one step closer to advancing care for women in the US who experience VMS,” said Ahsan Arozullah, MD, MPH, Senior Vice President and Head of Development Therapeutic Areas, Astellas. “We look forward to the FDA’s review of our application, and the potential to offer a first-in-class nonhormonal treatment option to reduce the frequency and severity of moderate to severe VMS associated with menopause.”

References

  1. U.S. FDA accepts Astellas’ New Drug Application for fezolinetant. News release. Astellas Pharma Inc. Accessed August 18, 2022. https://www.prnewswire.com/news-releases/us-fda-accepts-astellas-new-drug-application-for-fezolinetant-301608116.html
  2. Astellas to present 12-week data from pivotal phase 3 SKYLIGHT 1 trial of fezolinetant in oral session at the American College of Obstetricians and Gynecologists Annual Meeting. News release. Astellas Pharma Inc. May 6, 2022. Accessed August 18, 2022. https://www.astellas.com/en/news/25781
  3. 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. September 22, 2021. Accessed August 18, 2022. https://www.astellas.com/en/news/17176