What kind of medicine is Veozah?

Veozah is an oral, small molecule neurokinin 3 receptor (NK3R) antagonist developed by Astellas Pharma Inc for the treatment of moderate to severe vasomotor symptoms (VMS) or menopausal hot flashes.

Inhibiting NK3R-mediated signaling in the central nervous system is a non-hormonal strategy to modulate neuronal activity related to thermoregulation, thereby reducing the frequency and severity of VMS. Veozah was first approved in the United States in May 2023 for the treatment of moderate to severe VMS caused by menopause.

What medicine is it?

Veozah is an NK3 (neurokinin 3) receptor antagonist. NK3 receptors play an important role in regulating body temperature in the human brain. The US FDA approved Veozah (fezolinetant) on May 12, 2023, for the treatment of moderate to severe vasomotor symptoms (hot flashes) in perimenopausal women.

Vasomotor symptoms (VMS) are a common painful experience during menopause, affecting a significant number of women. Hormone therapy (HT) is the traditional treatment, but its limitations and potential risks have led to research into non-hormone replacement therapies. Recently, the FDA approved Veozah (felinetan) as a promising non-hormonal solution for moderate to severe VMS in menopause.

Veozah is an innovative neurokinin 3 (NK3) receptor antagonist that targets the disrupted thermoregulation under VMS. It modulates neural activity within the thermoregulatory center by crossing the blood-brain barrier, relieving hot flashes and night sweats. Clinical trials including SKYLIGHT 1TM, SKYLIGHT 2TM and SKYLIGHT 4TM have established the efficacy and safety of Veozah.

The recommended dose of 45 mg tablet per day shows proportional pharmacokinetics and side effects are generally mild and require regular monitoring. Veozah is the first FDA-approved drug in the NK3 receptor antagonist class to treat hot flashes in perimenopausal women, and the oral availability of Veozah makes it a convenient and accessible option for women seeking relief from VMS.

Veozah for the treatment of vasomotor disease

Background: Neurokinin 3 receptor antagonists are potential non-hormonal therapies for the treatment of vasomotor symptoms in menopausal women because there are few options for those who cannot or do not want to undergo hormonal therapy. Veozah is the first non-hormonal neurokinin 3 receptor antagonist in development for the treatment of vasomotor symptoms associated with menopause.

Methods: SKYLIGHT1 was a randomized, double-blind, placebo-controlled, 12-week Phase 3 trial with a 40-week extension to active treatment. The trial is being conducted at 97 institutions in the United States, Canada, Poland, Spain and the United Kingdom. Women aged 40-65 years who had an average of seven or more moderate to severe hot flashes per day were randomly assigned (1:1:1) to a once-daily fully matched placebo, Veozah 30 mg, or Veozah 45 mg. The primary endpoint was the mean change in frequency and severity of vasomotor symptoms from baseline to weeks 4 and 12.

Results: 2205 women were recruited, 175 were assigned to the placebo group, 176 to the Veozah 30 mg group, and 176 to the Veozah 45 mg group (175 in the placebo group, 174 in the Veozah 30 mg group, and 173 in the Veozah 45 mg group received at least one dose). One subject randomly assigned to take Veozah 45 mg mistakenly took Veozah 30 mg, so the efficacy analysis set consisted of 173 people in the Veozah 30 mg group and 174 people in the Veozah 45 mg group. Twenty-three participants in the placebo group, 31 participants in the 30 mg Veozah group, and 13 participants in the 45 mg Veozah group discontinued treatment before Week 12, primarily due to adverse events or participant withdrawal.

Veozah 30mg and Veozah 45mg significantly reduced the frequency of vasomotor symptoms compared with placebo at week 4. Veozah 30mg and 45mg significantly reduced the severity of vasomotor symptoms compared with placebo at week 4. Improvements in the frequency and severity of vasomotor symptoms were observed after 1 week and were maintained over 52 weeks.

During the first 12 weeks, 65 of 174 (37%) women in the Veozah 30 mg group, 75 of 173 (43%) women in the Veozah 45 mg group, and 78 of 175 (45%) women in the placebo group experienced an adverse event. The incidence of liver enzyme elevations is low, and these events are usually asymptomatic, transient, and resolve during treatment or after treatment interruption.

CONCLUSIONS: Veozah is a well-tolerated and effective non-hormonal therapy that rapidly reduces VMS in moderate/severe postmenopausal women.

Effects of Veozah on Endometrial Health

One study evaluated Veozah's safety and effects on endometrial health over 52 weeks. Methods: A 52-week Phase 3, randomized, double-blind safety study was conducted with placebo, Veozah 30 mg, and Veozah 45 mg once daily (1:1:1). The primary endpoints were treatment-emergent adverse events, percentage of participants with endometrial hyperplasia, and percentage of participants with endometrial malignancy. Endometrial hyperplasia or malignancy was assessed according to U.S. Food and Drug Administration guidelines (point estimate 1% or less, upper limit of one-sided 95% confidence interval 4% or less). Secondary endpoints included changes in bone mineral density (BMD) and trabecular bone score. The sample size was calculated to be 1,740 in order to be able to observe one or more events (the probability of an event with a background rate less than 1% is approximately 80%).

Results: A total of 1830 participants were randomized to receive one or more drug doses. Treatment-emergent adverse events occurred in 64.1% (391/610) of the placebo group, 67.9% (415/611) of the Veozah 30 mg group, and 63.9% of the Veozah 45 mg group.

(389/609). Treatment emergencies leading to discontinuation were similar across groups.

Endometrial safety was assessed in 599 participants. Endometrial hyperplasia occurred in 1 of 203 participants in the Veozah 45-mg group, and there were no cases in the placebo group (0/186) or the 30-mg Veozah group (0/210). One of the 210 patients in the Veozah 30 mg group developed endometrial malignant tumors, and there were no cases in the other groups. Six of 583 patients in the placebo group, 8 of 590 patients in the Veozah 30 mg group, and 12 of 589 patients in the Veozah 45 mg group had liver enzyme elevations more than three times the upper limit of normal. No cases of Hay's law were reported (i.e., no severe drug-induced liver injury, alanine aminotransferase or aspartate aminotransferase more than 3 times the upper limit of normal, total bilirubin more than 2 times the upper limit of normal, no alkaline phosphatase elevation, and no other explanation for the combination). Changes in BMD and trabecular bone scores were similar between groups.

Taken together, the results from SKYLIGHT 4 confirm the safety and tolerability of Veozah over 52 weeks.

Summary

Veozah is a drug used to treat moderate to severe vasomotor symptoms caused by menopause. During treatment, patients should be informed that blood tests must be performed to evaluate their liver before starting treatment with Veozah and at 3, 6, and 9 months of treatment with Veozah, and when clinically indicated to evaluate symptoms of abnormal liver symptoms (such as nausea, vomiting, or yellowing of the skin or eyes).

Recommended related articles: