Elinzanetant Reduces Hot Flashes In Menopause

A yearlong shape 3 proceedings shows elinzanetant tin trim basking flashes by astir three-quarters while maintaining a beardown information profile, positioning it arsenic a promising caller action for women seeking alternatives to hormone therapy.

Study: Elinzanetant for nan Treatment of Vasomotor Symptoms Associated With Menopause. Image credit: New Africa/Shutterstock.com

A caller study in JAMA Internal Medicine investigated nan information and efficacy of elinzanetant for treating mean to terrible vasomotor symptoms (VMS) successful menopausal women, successful a shape 3 Randomized Clinical Trial (RCT).

Vasomotor symptoms and accepted treatments

VMS, commonly known arsenic basking flashes, are disruptive menopause-associated symptoms that women acquisition during nan time aliases night, on pinch sweating and slumber disturbance. Up to 80% women acquisition VMS, and up to 60% study slumber disturbances, some of which adversely power their value of life.

Although hormone therapy (HT) is commonly recommended to alleviate menopausal symptoms, it is not suitable for each women. In galore countries, antidepressants are besides utilized to dainty VMS. Previous investigation has shown that these treatments person humble efficacy compared to a placebo. Additionally, various factors, including tolerability issues, lead to expanding curen discontinuation rates, peculiarly during nan first 3 months. Since VMS tin past a mean of 7 to 10 years, an replacement effective involution is urgently needed.

During and aft nan menopausal transition, estrogen levels deplete, starring to hypertrophy and hyperactivity of hypothalamic kisspeptin/neurokinin B/dynorphin (KNDy) neurons. This hyperactivity is accompanied by an overexpression of neurotransmitters, including neurokinin B (NKB) and constituent P (SP). This hyperactivation correlates pinch nan thermoregulatory disruption successful VMS. SP and NK-1 receptors whitethorn person a domiciled successful peripheral vasodilatation and superior insomnia.

In galore countries, nan NK-3 receptor antagonist fezolinetant has been approved for nan curen of mean to terrible VMS owed to menopause. Recent shape 3 trials, OASIS-1 and OASIS-2, person assessed nan information and efficacy of elinzanetant, an antagonist of NK-1 and NK-3 receptors. During nan 26-week study period, a important simplification successful VMS wave was observed, pinch reductions evident by week 1 of receiving elinzanetant treatment.

About nan study

The existent study documented the 52-week OASIS-3 study, nan first Phase 3 objective proceedings to measure nan information and efficacy of elinzanetant for treating VMS beyond 6 months of usage successful postmenopausal women. OASIS-3 was conducted astatine 83 sites crossed North America and Europe betwixt August 27, 2021, and February 12, 2024.

Naturally aliases surgically postmenopausal women, betwixt nan ages of 40 and 65 years, were selected. All women sought curen to alleviate mean to terrible VMS. Participants pinch abnormal liver parameters, endometrial polyps, hyperplasia, disordered proliferative endometrium, aliases malignant neoplasm were excluded. Unlike OASIS-1/-2, OASIS-3 had nary minimum VMS wave requirement, broadening generalizability.

Eligible candidates were randomly assigned successful a 1:1 ratio to either nan curen aliases placebo groups. The curen group participants received 120 mg of elinzanetant orally for nan full 52-week study duration.

All participants maintained an physics basking flash regular diary (HFDD). They besides completed nan Patient-Reported Outcomes Measurement Information System Sleep Disturbance Short Form 8b full T people and Menopause-Specific Quality Of Life (MENQOL) questionnaire full people complete 52 weeks. For information assessment, participants were asked to spontaneously study immoderate adverse events (AEs) they knowledgeable during nan study.

Study findings

A full of 1,524 women were screened, of whom 628 were randomized to nan elinzanetant and placebo groups. The mean property of nan participants was 54.7 years. At baseline, nan demographic characteristics of nan participants of some groups were good balanced.

At baseline, women successful nan elinzanetant and placebo arms knowledgeable 6.7 and 6.8 mean to terrible VMS events per day, respectively. After 12 weeks (the superior endpoint clip point) of intervention, nan mean alteration was −5.4 for nan elinzanetant limb and −3.5 for nan placebo arm.

The existent study estimated nan least-squares (LS) mean quality successful nan alteration from baseline for elinzanetant compared pinch placebo astatine week 12 to beryllium −1.6. In addition, descriptive analyses indicated that astatine a akin time, nan mean percent changes were −73.8% for elinzanetant and −47.0% for placebo. Notably, aft 50 weeks of intervention, participants knowledgeable a mean of 1.4 and 3.5 mean to terrible VMS events per time successful nan elinzanetant and placebo arms, respectively.

Secondary and exploratory outcomes were analyzed descriptively, including slumber and MENQOL complete 52 weeks and VMS complete 50 weeks. The proceedings was not powered to observe between-group differences connected these endpoints.

Baseline mean Patient-Reported Outcomes Measurement Information System Sleep Disturbance Short Form SF 8b full T-scores were 57.4 for elinzanetant and 58.0 for placebo. Mean baseline MENQOL full scores were 4.1 for elinzanetant and 4.4 for placebo.

At nan extremity of nan study period, 70.0% and 61.1% of women successful nan elinzanetant and placebo arms, respectively, knowledgeable astatine slightest 1 treatment-emergent AE (TEAE). Approximately, 89% of nan TEAEs successful nan elinzanetant limb and 89.6% successful nan placebo limb were mild aliases mean successful intensity. In some nan study arms, nan commonly reported TEAEs were headache, nasopharyngitis, COVID-19, fatigue, and somnolence.

A comparatively debased discontinuation complaint was recorded astatine 12.5% successful nan elinzanetant limb and 4.1% successful nan placebo arm, though discontinuation was higher successful nan curen group, chiefly owed to adverse events. No endometrial hyperplasia aliases malignant endometrial neoplasms were observed successful nan endometrial biopsy successful some arms. Only 2 participants successful nan elinzanetant limb had clinically important abnormal mammogram reports.

After nan 52-week study period, serum concentrations of estradiol, luteinizing hormones, progesterone, and follicle-stimulating hormones did not importantly change. Furthermore, assemblage weight and creation remained unchangeable successful some groups astatine nan extremity of nan study period. Some liver enzyme elevations occurred successful some arms (a fewer met predefined monitoring criteria), but location were nary Hy’s rule cases, and nan independent committee concluded nary hepatotoxic signal.

Conclusions

The existent study highlighted a favorable efficacy and information floor plan of elinzanetant aft 52 weeks of treatment. This curen resulted successful a simplification successful nan number of regular VMS events compared to nan placebo. Notably, elinzanetant was recovered to beryllium well-tolerated successful menopausal women pinch mean to terrible VMS.

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