Nonhormonal drug reduces hot flash severity, symptoms in menopause
Menopausal women experiencing moderate to severe vasomotor symptoms randomly assigned to an oral, nonhormonal compound for 12 weeks experienced fewer weekly hot flashes and reduced symptom severity across doses compared with similar women assigned placebo, according to findings presented at the North American Menopause Society annual meeting.
Data from the phase 2b study also demonstrated that women assigned fezolinetant (Astellas Pharma) experienced improvements in patient-reported outcomes, including a 50% or greater reduction in vasomotor symptoms.
“Up to 80% of menopausal women experience vasomotor symptoms, which result from loss of thermoregulatory control,” Nanette Santoro, MD, professor and chair of reproductive endocrinology and infertility, department of obstetrics and gynecology at the University of Colorado Denver, and colleagues wrote in an abstract. “Fezolinetant is a neurokinin 3 receptor antagonist that modulates the function of kisspeptin/neurokinin B/dynorphin neurons in the hypothalamus, which is responsible for thermoregulation. This study evaluated the effect of fezolinetant on vasomotor symptoms and patient-reported outcomes.”
In a double-blind study, Santoro and colleagues analyzed data from 356 women aged 40 to 65 years with moderate to severe vasomotor symptoms ( 50 hot flashes per week; mean age, 54 years; 73% white). Researchers randomly assigned participants to fezolinetant 15 mg, 30 mg, 60 mg or 90 mg twice daily, fezolinetant 30 mg, 60 mg or 120 mg once daily or placebo. Coprimary efficacy outcomes were changes in frequency and severity of vasomotor symptoms at weeks 4 and 12; secondary endpoints included response ( 50% reduction in vasomotor symptoms) and changes in scores for the Hot Flash-Related Daily Interference Scale (HFRDIS), the Greene Climacteric Scale (GCS), and the Menopause-Specific Quality of Life (MENQoL) questionnaire at weeks 4 and 12.
Within the cohort, 352 women received at least one dose of the study drug and 287 women (81%) completed the study.
Compared with placebo, researchers found that fezolinetant reduced daily hot flash frequency across all doses, with least squares mean differences ranging from 1.9 to 3.5 at week 4 and from 1.8 to 2.6 at week 12 (P < .05 for all). Hot flash severity scores were also reduced for women assigned fezolinetant vs. placebo across all doses, with least squares mean differences ranging from 0.4 to 1 at week 4 (P < .05 for all) and ranging from 0.2 to 0.6 at week 12 (P < .05 for all).
Women assigned fezolinetant were also more likely to experience a 50% or greater reduction in hot flashes at the last on-treatment assessment, with mean reductions of 83.7% for the 15 mg, 81.4% for the 30 mg, 88.1% for the 60 mg and 94.7% for the 90 mg twice-daily doses, and mean reductions of 82.1% for the 30 mg, 88.1% for the 60 mg and 84.1% for the 120 mg once-daily doses. Women assigned placebo reported a mean 58.5% reduction in hot flashes at the last on-treatment assessment (P < .05 for all)
In assessing patient-reported outcomes, researchers found that changes from baseline for the three questionnaires exceeded published minimum important difference values at weeks 4 and 12.
“Fezolinetant reduced frequency and severity of vasomotor symptoms, which was accompanied by clinically meaningful improvements in patient-reported outcomes,” the researchers wrote.
In August, Astellas Pharma announced that dosing for the first patients in the phase 3 trial for fezolinetant had begun.
“There are currently limited nonhormonal options for managing vasomotor symptoms, which can be quite disruptive and often interfere with daily life,” Salim Mujais, MD, senior vice president and therapeutic area head of medical specialties for Astellas, said in a press release announcing the phase 3 study. “With the initiation of our phase 3 fezolinetant program, we move further toward our goal of providing women with a nonhormonal treatment for moderate to severe hot flashes.” – by Regina Schaffer
Santoro N, et al. Abstract S-11. Presented at: North American Menopause Society Annual Meeting; Sept. 25-28, 2019; Chicago.
Disclosure: Astellas Pharma funded this study.