How effective is the hot flash drug veozah (filazonetant)?

SKYLIGHT 1 was a randomized, double-blind, placebo-controlled, 12-week Phase 3 trial (NCT04003155) that extended the active treatment period to 40 weeks. The trial was conducted at 97 institutions in the United States, Canada, Czech Republic, Hungary, Poland, Spain and the United Kingdom. Women aged 40 to 65 years with an average of 7 or more moderate to severe hot flashes per day were randomly assigned (1:1:1) to receive exactly matched placebo, 30 mg of Veozah (fezonatan), or 45 mg of Veozah (fezonatan) once daily.

Randomization was performed using a web-based interactive response system, with researchers, project team members, clinical staff, and participants masked to treatment allocation. The co-primary endpoint was the mean change in frequency and severity of vasomotor symptoms from baseline to weeks 4 and 12. Efficacy and safety analyzes included all randomly assigned participants who received at least one dose of study drug.

Study results: 2205 women were recruited, 175 were assigned to placebo, 176 to 30 mg of fezolintan, and 176 to 45 mg of fezolintan (175 in the placebo group, 174 in the 30 mg group, and 173 in the 45 mg veozah (fazolintan) group received at least one dose [safety analysis set]).

One participant randomized to 45 mg of veozah mistakenly received 30 mg of veozah, so the efficacy analysis set (full analysis set) consisted of the 173 mg veozah group and the 174 mg veozah group. Twenty-three participants in the placebo group, 31 participants in the 30 mg veozah (fezonatan) group, and 13 participants in the 45 mg veozah (fezonatan) group discontinued treatment before Week 12, primarily due to adverse events or participant withdrawal.

Veozah (felzonitant) 30 mg and 45 mg significantly reduced the frequency of vasomotor symptoms at weeks 4 and 12 compared with placebo. Fezolintan 30 mg and 45 mg significantly reduced the severity of vasomotor symptoms compared with placebo at weeks 4 and 12. Improvements in frequency and severity of vasomotor symptoms were observed after 1 week and maintained through 52 weeks.

During the first 12 weeks, treatment-emergent disease occurred in 65 of 174 (37%) women in the veozah 30 mg group, 75 of 173 (43%) in the veozah 45 mg group, and 78 of 175 (45%) in the placebo group. The incidence of liver enzyme elevations was low (placebo n=1; Veozah 30 mg n=2; Veozah 45 mg n=0), and these events were generally asymptomatic, transient, and resolved during treatment or after discontinuation of treatment.

Conclusions: Data support the clinical use of non-hormonal treatments for vasomotor symptoms associated with menopause.

At present, veozah (filazonetant) is suitable for the treatment of moderate to severe vasomotor symptoms caused by menopause and has been approved for marketing. It is recommended that patients take medication as directed by their doctor and receive symptomatic treatment.

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References

Lederman S, Ottery FD, Cano A, Santoro N, Shapiro M, Stute P, Thurston RC, English M, Franklin C, Lee M, Neal-Perry G. Fezolinetant for treatment of moderate-to-severe vasomotor symptoms associated with menopause (SKYLIGHT 1): a phase 3 randomized controlled study. Lancet. 2023 Apr 1;401(10382):1091-1102. doi: 10.1016/S0140-6736(23)00085-5. Epub 2023 Mar 13. PMID: 36924778.