A recent meta-analysis published in PubMed indicates that both fezolinetant and elinzanetant are effective in reducing vasomotor symptoms (VMS) in menopausal women. The study, which analyzed data from seven randomized controlled trials (RCTs) involving 4,087 patients, highlights the potential of these drugs to improve the quality of life for women experiencing menopause.
The analysis focused on the efficacy and safety of fezolinetant and elinzanetant in alleviating VMS, which include hot flashes and night sweats. These symptoms are reported by up to 80% of women during menopause and can significantly impair health-related quality of life, affecting sleep, concentration, mood, and energy levels.
Efficacy in Reducing Vasomotor Symptoms
The meta-analysis revealed that both fezolinetant and elinzanetant were associated with a significant reduction in the frequency of vasomotor symptoms. Specifically, fezolinetant at 30 mg showed a mean difference of 2.16 (95% CI, 1.54-2.79, I2=0%), while fezolinetant at 45 mg showed a mean difference of 2.54 (95% CI, 1.86-3.21, I2=0%). Elinzanetant at 120 mg demonstrated a mean difference of 2.99 (95% CI, 1.74-4.23, I2=0%).
In terms of symptom severity, both drugs also showed a notable decrease: fezolinetant 30 mg (mean difference 0.20, 95% CI, 0.09-0.33, I2=0%), fezolinetant 45 mg (mean difference 0.24, 95% CI, 0.13-0.34, I2=0%), and elinzanetant 120 mg (mean difference 0.36, 95% CI, 0.26-0.46, I2=0%).
Impact on Sleep Quality
Elinzanetant at 120 mg was found to significantly improve sleep quality, with a mean difference of 4.65 (95% CI, 3.73-5.56, I2=0%). This is a particularly important finding, as sleep disturbances are a common and distressing symptom of menopause.
Safety and Tolerability
While both drugs were generally well-tolerated, elinzanetant 120 mg was associated with a higher occurrence of drug-related adverse events (20.75% vs 11.70%, risk ratio [RR] 0.57, 95% CI, 0.39-0.82, I2=19%) and headache (8.0% vs 2.54%, RR 0.32, 95% CI, 0.16-0.64, I2=0%).
Fezolinetant's Safety Profile Confirmed in Pooled Analysis
A separate pooled analysis of three Phase 3 trials (SKYLIGHT 1, 2, and 4) further confirmed the safety and tolerability of fezolinetant over 52 weeks. The analysis, which included nearly 3000 women with VMS, showed a low incidence of drug-related serious treatment-emergent adverse events (TEAEs) and infrequent elevations in liver transaminases, which were generally asymptomatic.
According to the study published in springermedizin.de, elevations in ALT and/or AST > 3x ULN occurred in 2.3% of participants treated with fezolinetant 45 mg and 1.5% of the fezolinetant 30 mg group, compared with 0.9% of those treated with placebo. The independent review by a liver safety monitoring panel concluded that cases appear to be rare in fezolinetant-treated patients, with no specific pre-disposing characteristics identified.
Endometrial Safety and Malignancy Risk
The pooled analysis also addressed concerns about endometrial safety and malignancy risk. After 52 weeks of treatment, there was a single case of endometrial hyperplasia (0.3%) in the fezolinetant 30 mg group and two cases (0.6%) in the fezolinetant 45 mg group. A single case of endometrial malignancy (0.3%) was reported in the fezolinetant 30 mg group. These results were well within the FDA criterion for endometrial safety.
An in-depth post hoc analysis of non-benign neoplasms in SKYLIGHT 4 did not support a drug effect for increased risk, considering short latency periods to diagnosis, tumor type heterogeneity, prior neoplastic/risk factor history, and presence of alternative baseline etiologies. The FDA and EMA have also reviewed the data and found insufficient evidence to support an increased risk of malignancy with fezolinetant.
Clinical Implications
The findings from these studies suggest that fezolinetant and elinzanetant are valuable options for managing vasomotor symptoms in menopausal women. While hormone therapy remains a primary treatment, these non-hormonal alternatives offer important options for women who are not candidates for hormone therapy or prefer non-hormonal treatments. Elinzanetant's additional benefit in improving sleep quality may make it a particularly attractive option for women struggling with sleep disturbances during menopause.
