Fezolinetant is a non-hormonal treatment modality that is safe and effective over 52 weeks for treating moderate-to-severe vasomotor symptoms in menopausal women.
Menopausal hormone therapy effectively manages vasomotor symptoms in some individuals, but not all women are candidates for hormonal therapy. Fezolinetant is a non-hormonal neurokinin 3 receptor antagonist that works by moderating activity in the thermoregulatory center in the hypothalamus.
This clinical trial, published in the journal Obstetrics and Gynecology, evaluated the tolerability, safety, and effectiveness of fezolinetant on endometrial health. The study confirmed the efficacy and long-term safety of fezolinetant for treating menopause-related vasomotor symptoms.
The total number of study participants was 1830, of which 610 were assigned to the placebo group, 609 in the fezolinetant 45 mg group, and 611 in the fezolinetant 30 mg group. The median treatment duration was 364.0 days. A total of 599 study participants were present in the endometrial health set.
Treatment-Emergent Adverse Events
The incidence of common adverse events was similar across the treatment groups, whereas serious adverse events were low and observed in 2.3% of participants in the placebo, 3.3% of participants in the fezolinetant 30 mg, and 3.8% of participants in the fezolinetant 45 mg groups. In the fezolinetant 30 mg group, one patient died of anoxic brain injury, cardiac arrest, and delayed airway access; however, these events were not associated with the treatment.
Impact on Endometrial Health and Safety
In the endometrial health set, endometrial hyperplasia was reported only in one patient in the fezolinetant 45 mg group. Conversely, endometrial malignancy was reported in one patient in the fezolinetant 45 mg group. The placebo group and fezolinetant group patients did not exhibit any significant differences in the transvaginal ultrasonography-determined endometrial thickness. There was a greater prevalence of uterine bleeding among the placebo group participants. Four participants in the placebo group and three participants in the fezolinetant 30 mg group demonstrated a disordered proliferative pattern, diagnosed via biopsy.
Low Fracture Incidence and Consistent Bone Changes in Fezolinetant
The incidence of bone fractures was low, and there were consistent changes in the trabecular bone score and bone mineral density of the spine and hip across treatment and placebo group participants. An increase in the levels of aspartate aminotransferase and alanine aminotransferase was observed in six placebo group participants, eight fezolinetant 30 mg group participants, and 12 fezolinetant 45 mg group participants.
In conclusion, fezolinetant 30 mg and fezolinetant 45 mg are safe and tolerable in menopausal patients experiencing vasomotor symptoms. The severity of treatment-emergent adverse events is mild to moderate, and the risk of malignancy or hyperplasia of the endometrium is within the limits specified previously.
Neal-Perry, G., Cano, A., Lederman, S., Nappi, R. E., Santoro, N., Wolfman, W., English, M., Franklin, C., Valluri, U., & Ottery, F. D. (2023). Safety of Fezolinetant for Vasomotor Symptoms Associated With Menopause. Obstetrics & Gynecology, 141(4), 737–747. https://doi.org/10.1097/aog.0000000000005114