A New Horizon for Menopausal Hot Flashes
For decades, hormone replacement therapy (HRT) has been a primary treatment for menopausal hot flashes, but it comes with potential risks that make it unsuitable for all women. The 2023 approval of Veozah represented a significant breakthrough by offering a non-hormonal alternative that directly targets a key neurological pathway involved in temperature regulation. Developed by Astellas Pharma, Veozah (fezolinetant) is the first-in-class selective neurokinin 3 (NK3) receptor antagonist designed to address the root cause of VMS in the brain.
The Pharmacology Behind Fezolinetant
Unlike HRT, which introduces hormones to the body, Veozah uses a different mechanism of action. During menopause, declining estrogen levels disrupt the brain's thermoregulatory center, the hypothalamus. This disruption leads to an overproduction of a neuropeptide called neurokinin B (NKB). When NKB binds to the NK3 receptor, it triggers the vasodilation and sweating that characterize a hot flash. Fezolinetant, Veozah's active ingredient, works by blocking NKB from binding to the NK3 receptor. This action helps to modulate and normalize the neuronal activity in the hypothalamus, thereby reducing the frequency and severity of hot flashes and night sweats.
Clinical Trials and Efficacy
The FDA's approval was based on robust clinical trial data from the BRIGHT SKY Phase 3 clinical program. Two pivotal trials, SKYLIGHT 1 and SKYLIGHT 2, evaluated the efficacy and safety of fezolinetant in over 1,000 postmenopausal women with moderate to severe hot flashes.
- Significant Reduction: In both trials, Veozah 45 mg demonstrated a statistically significant and clinically meaningful reduction in the frequency and severity of VMS compared to a placebo at both week 4 and week 12.
- Fast-Acting Relief: Some women experienced a reduction in hot flashes within the first week of treatment, with sustained benefits observed throughout the trials.
- Long-Term Safety: The SKYLIGHT 4 trial evaluated the long-term safety profile of fezolinetant over 52 weeks, providing additional data to support its use.
Veozah vs. Hormone Replacement Therapy (HRT)
For many women, the choice between Veozah and HRT depends on their health profile and symptom priorities. This table compares the two treatment approaches.
| Feature | Veozah (Fezolinetant) | Hormone Replacement Therapy (HRT) |
|---|---|---|
| Mechanism | Non-hormonal; blocks neurokinin B (NKB) from binding to NK3 receptors in the brain's thermoregulatory center. | Hormonal; replenishes declining estrogen and, in some cases, progesterone levels during menopause. |
| Target Symptoms | Specifically targets and reduces the frequency and severity of moderate to severe hot flashes and night sweats (VMS). | Addresses a broader range of menopausal symptoms, including hot flashes, vaginal dryness, and bone density loss. |
| Key Benefit | Offers a non-hormonal alternative for women who cannot or choose not to take HRT due to medical risks. | Historically the most comprehensive treatment for a wide range of menopausal symptoms. |
| Contraindications | Known cirrhosis, severe kidney problems or failure, and concomitant use with CYP1A2 inhibitors. | History of hormone-sensitive cancers (e.g., breast cancer), blood clots, or certain types of heart disease. |
Important Safety Considerations
In December 2024, the FDA issued a Drug Safety Communication and added a Boxed Warning to the Veozah product label regarding the risk of rare but serious liver injury. This serious warning was based on postmarketing reports and emphasizes the need for consistent monitoring.
Monitoring Requirements
- Baseline Testing: Before beginning Veozah, patients must undergo baseline bloodwork to evaluate liver function.
- Follow-up Testing: Liver function tests should be repeated monthly for the first three months of treatment, and then again at months 6 and 9.
- Immediate Action: Patients must contact their healthcare provider immediately if they experience signs of liver problems, such as unusual fatigue, nausea, vomiting, or jaundice.
Potential Side Effects
Clinical trials identified the most common side effects of Veozah as:
- Abdominal pain
- Diarrhea
- Insomnia
- Back pain
- Elevated hepatic transaminases (liver enzymes)
Conclusion
Veozah's approval on May 12, 2023, expanded the options available for women seeking relief from menopausal hot flashes. As the first non-hormonal NK3 receptor antagonist, it offers a new pathway for modulating the brain's thermoregulatory center, providing an important alternative for those who cannot or prefer not to use HRT. While its efficacy is well-supported by clinical trials, the medication carries a significant boxed warning regarding liver injury, underscoring the critical need for regular monitoring throughout treatment. For many, Veozah represents a valuable and targeted advancement in the treatment of menopause-related vasomotor symptoms. For more information on the FDA's press release concerning Veozah, you can find the official announcement here.
