CHICAGO — Fezolinetant, a treatment for women with moderate to severe vasomotor symptoms associated with menopause, showed improvements in frequency and severity of symptoms compared with placebo, a researcher said here.
Women randomized to fezolinetant at a range of doses, either daily or twice a day, had a 75-87% reduction in the frequency of vasomotor symptoms from baseline to week 12, which was significant compared with placebo (55% reduction), reported Nanette Santoro, MD, of the University of Colorado School of Medicine in Aurora.
Fezolinetant also showed clinically meaningful changes in patient-reported outcomes, and the drug seemed safe and well tolerated across dosing groups, she added.
At a presentation at the North American Menopause Society annual meeting, Santoro noted that vasomotor symptoms, such as hot flashes and night sweats, are reported by up to 80% of U.S. women who go through menopause. A loss of thermoregulatory control in an area of the brain with neurokinin 3 receptor (NK3R)-expressing neurons is believed to cause these symptoms, she noted.
Fezolinetant is an oral NK3R agonist that has previously shown reduced frequency and severity of symptoms in patients with moderate to severe vasomotor symptoms over the course of an earlier 12-week trial. The current phase IIb trial was designed to examine the efficacy of a range of doses and regimens of the drug, as well as look at patient-reported outcomes to the treatment, and examine its safety and tolerability.
Participants were postmenopausal women ages 40-65 with at least 50 moderate to severe vasomotor symptoms a week and a body mass index of 18-38. Over a 12-week treatment period, patients were randomized to receive fezolinetant at a dose of either 15, 30, 60, or 90 mg twice a day; or 30, 60, 90, or 120 mg dose once a day; or placebo.
There was no significant difference between groups in patient characteristics: women were a mean age of around 55, with a BMI ranging from 27 to 29, and the majority of participants were white. Overall, 352 women received at least one dose of the study drug, and 287 of those completed the study.
Santoro noted there was a large placebo effect in the study, with a “robust 55%” reduction for the placebo group in symptom reduction. This continued, even when examining secondary outcomes, such as the effect on “responders” (defined as women who had at least a 50% reduction from baseline in frequency of moderate to severe vasomotor symptoms). In this group, reductions in symptoms ranged from 82% to 95% of the treatment groups, with a “whopping portion” of the placebo group (59%) also reporting a reduction in symptoms, Santoro said.
In addition, she said, there was a suggestion of a dose-response effect, as the group reporting the greatest reduction in symptoms was the group receiving the 120 mg dose of the study drug twice a day.
For the study, the team derived patient-reported outcomes from the Menopause-Specific Quality of Life (MENQoL) questionnaire, Hot Flash-Related Daily Interference Scale (HFRDIS), and the Greene Climacteric Scale. All doses of fezolinetant improved HFRDIS and MENQoL scores, and GCS-VMS scores were improved for most doses of fezolinetant at weeks 4 and 12 relative to placebo, Santoro reported.
Treatment-related adverse events were comparable across the groups, and most were mild or moderate, she said. There were no deaths in any group. The researchers also examined liver function, noting that all patients were asymptomatic, with no cases of Hy’s Law. There were also no other clinically meaningful changes in vital signs, laboratory tests, electrocardiogram parameters, or plasma bone marker concentration, and no evidence of suicidal ideation, the authors said.
This study was supported by Astellas Pharma Inc.
Santoro disclosed support from Ogeda and MenoGeniX, Inc.; other co-authors disclosed support from Radius Health, Ogeda, Mitsubishi Pharma, MenoGeniX , Endoceutics, Shionogi, Altus Research, as well as being employed or formerly employed by Ogeda and Astellas Pharma.
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