What is Veozah (Fezolinetant)?
Veozah (fezolinetant) is an FDA-approved, oral neurokinin 3 (NK3) receptor antagonist indicated for the treatment of moderate to severe vasomotor symptoms (hot flashes and night sweats) due to menopause, representing the first non-hormonal medication in this novel drug class. 1
Mechanism of Action
- Fezolinetant works by blocking NK3 receptors in the central nervous system, specifically targeting the thermoregulatory center in the hypothalamus that becomes dysregulated during menopause 2, 3
- Unlike hormone therapy, it crosses the blood-brain barrier to directly modulate neural activity controlling body temperature without affecting estrogen levels 2
- This non-hormonal mechanism makes it particularly valuable for women who cannot or prefer not to use hormone therapy 3
Clinical Efficacy
Fezolinetant demonstrates robust efficacy in reducing both frequency and severity of vasomotor symptoms, with benefits appearing within the first week of treatment:
- At the recommended 45 mg daily dose, fezolinetant reduces hot flash frequency by approximately 2.5 episodes per day compared to placebo at both week 4 and week 12 4, 5
- Severity of vasomotor symptoms is reduced significantly, with improvements maintained through 52 weeks of treatment 4, 5
- Meta-analysis confirms consistent reductions in VMS frequency (SMD = -0.64 at week 4, -0.63 at week 12) and severity scores (SMD = -0.59 at week 4, -0.40 at week 12) 6
- Quality of life improvements are measurable and clinically meaningful, with positive effects on menopause-specific quality of life scores 6
Dosing and Administration
- The recommended dose is one 45 mg tablet taken orally once daily 1
- A 30 mg dose was also studied and showed efficacy, though the 45 mg dose demonstrated superior reductions in vasomotor symptoms 4, 5
- The medication demonstrates proportional pharmacokinetics and convenient once-daily oral administration 2
Safety Profile
Fezolinetant is generally well-tolerated with mostly mild side effects, though liver enzyme monitoring is required:
- Treatment-emergent adverse events in the first 12 weeks occurred in 43% of patients on fezolinetant 45 mg versus 45% on placebo, indicating similar overall tolerability 5
- Specific adverse events more common with fezolinetant include fatigue (RR = 4.05), arthralgia (RR = 2.83), and drug-related adverse events overall (RR = 1.47) 6
- Liver enzyme elevations (ALT or AST >3 times upper limit of normal) occur more frequently than placebo (RR = 2.0) but are generally asymptomatic, transient, and resolve either during continued treatment or after discontinuation 6, 5
- Serious treatment-emergent adverse events are infrequent, reported in only 1% of patients receiving fezolinetant 45 mg 4
Clinical Positioning
Veozah represents an important addition to the treatment armamentarium for menopausal vasomotor symptoms, particularly for specific patient populations:
- It serves as a viable alternative to hormone therapy for women with contraindications to estrogen (history of breast cancer, thromboembolic disease, stroke) or those who prefer non-hormonal options 7, 8, 6
- Current guidelines recommend non-hormonal pharmacologic treatments as first-line therapy for many women, particularly cancer survivors, with established options including SSRIs/SNRIs (venlafaxine, paroxetine), gabapentin, and clonidine 7, 8
- Fezolinetant's efficacy appears comparable to or potentially superior to these established non-hormonal agents, though direct head-to-head trials are lacking 6
- Unlike SSRIs/SNRIs, fezolinetant has no known drug interactions with tamoxifen, making it potentially advantageous for breast cancer survivors on endocrine therapy 7, 8