SUN-150 - NOE-PMM-201, Results of Phase 2A Study of Cendifensine (NOE-115) for the Treatment of Vasomotor Symptoms in Menopausal Women

Introduction:

Within five years, an estimated 1.2 billion women worldwide will have experienced menopause, with up to 40% reporting moderate-to-severe vasomotor symptoms (VMS) requiring treatment. There remains a substantial need for effective non-hormonal therapies that address VMS and also common co-occurring symptoms, including mood disturbance, fatigue, food craving, and weight gain. Cendifensine (NOE-115) is a broad-spectrum monoamine modulator that targets dopamine, norepinephrine, and serotonin pathways in key brain regions involved in thermoregulation, mood, food craving, and sleep.

Methods:

NOE-PMM-201 (NCT06385795) was a multicenter, open-label, phase 2A study to evaluate safety and tolerability of cendifensine in menopausal women with VMS. Eligible participants with at least 7 moderate-to-severe hot flashes/day at baseline were enrolled. VMS frequency and severity were recorded using a daily hot flash diary; associated menopausal symptoms were assessed using validated self-reported scales. Safety assessments included adverse event (AE) monitoring, clinical laboratory testing, electrocardiograms (ECGs), and suicidality assessments. Participants were enrolled into three sequential cohorts: 15 mg 4-week cohort, 60 mg 12-week cohort, and 30 mg 12-week cohort.

Results:

Forty participants were enrolled maintaining a mean (SD) age of 54.1 (3.7) years, mean weight (SD) of 78.7 kg (15.5), mean body mass index (SD) of 29.3 kg/m² (5.2). At baseline, mean baseline moderate-to-severe VMS daily frequency (SD) was 12.7 (5.6), mean daily severity (SD) was 2.5 (0.4).

In the 30 mg 12-week cohort (n=18), treatment with cendifensine at Week 12 vs Baseline was associated with: moderate-severe VMS frequency 92.3% reduction (p < 0.001), and VMS severity 59.2% reduction (p < 0.001). The 60 mg cohort (n=17) demonstrated comparable efficacy, with 78.1% reduction in VMS frequency (p=0.016), and 45.6% reduction in VMS severity (p=0.031). Sensitivity analyses supported the robustness of these findings.

No serious adverse events were reported. AEs were mild to moderate in severity, with most common: dry mouth, headache, constipation, and insomnia. Across all dose levels, no clinically meaningful changes were observed in laboratory parameters, ECGs, or suicidality measures.

Statistically significant improvements (p < 0.05) were observed in co-occurring symptoms, including mood, fatigue, and food craving.

Conclusion/Implications:

In the NOE-PMM-201 study, cendifensine demonstrated robust reductions in VMS frequency and severity in menopausal women, with a favorable tolerability profile. Improvements in mood, fatigue, food craving, and weight suggest potential additional benefits relevant to the broader menopausal symptom spectrum. These encouraging open-label results support further evaluation of cendifensine in controlled clinical trials.

Funded by Noema Pharma

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