Positive topline results were announced from two phase 3 trials evaluating fezolinetant, an investigational, selective neurokinin-3 receptor (NK3R) antagonist, for the treatment of moderate to severe vasomotor symptoms (VMS) in postmenopausal women.
Fezolinetant works by inhibiting neurokinin B binding on the kisspeptin/neurokinin/dynorphin neuron to regulate neuronal activity in the thermoregulatory center in the hypothalamus. SKYLIGHT 1 (ClinicalTrials.gov: NCT04003155) and 2 (ClinicalTrials.gov: NCT04003142) are ongoing randomized, placebo-controlled, double-blind trials evaluating 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 (TEAE) for fezolinetant was headache. The incidence of serious TEAEs was reported to be less than 2% in patients treated with fezolinetant.
“We are encouraged by these results for fezolinetant, which mark the first phase 3 data in a new category of selective neurokinin-3 (NK3)-targeted treatments for moderate to severe vasomotor symptoms,” said Salim Mujais, MD, Senior Vice President and Therapeutic Area Head, Medical Specialties, Astellas.
Astellas announces positive topline results from two phase 3 pivotal global trials of fezolinetant for the nonhormonal treatment of vasomotor symptoms in postmenopausal women. [press release]. Tokyo, Japan: Astellas Pharma Inc; February 19, 2021.