SECOND NEUROKININ RECEPTOR ANTAGONIST APPROVED FOR MENOPAUSAL HOT FLASHES
Lynkuet joins Veozah as the second nonhormonal therapy approved for vasomotor symptoms (VMS)
Straight Healthcare
December 2025
December 2025
Lynkuet (elinzanetant), a nonhormonal treatment for vasomotor symptoms (VMS) due to menopause, was recently approved by the FDA. It is the second drug approved in the neurokinin (NK) receptor antagonists class, following Veozah (fezolinetant), approved in 2023. The drugs differ slightly in their NK receptor binding; Veozah selectively binds NK3 receptors while Lynkuet binds NK1 and NK3 receptors. During menopause, estrogen withdrawal increases neurokinin activity in the brain's thermoregulatory center, and NK receptor antagonists suppress neurokinin secretion.
In their respective phase 3 trials, both agents demonstrated a statistically significant reduction in VMS frequency and severity (≥ hot flashes over 24 hours) compared to placebo. In two 12-week trials, the placebo-subtracted reduction in VMS episodes (baseline ∼ 11 episodes/day) with Veozah was about 2.5 per 24 hours. Similarly, the placebo-subtracted reduction in VMS episodes (baseline ∼ 14 episodes/day) with Lynkuet was about 3.2 per 24 hours in 12-week trials. Notably, across all trials, the placebo group experienced reductions of 4 to 6 episodes per day, suggesting a significant psychological component in VMS improvement. Common side effects for both agents include gastrointestinal issues like abdominal pain and diarrhea, as well as nervous system effects such as insomnia, back pain, and headache. Lynkuet's label notes a central nervous system (CNS) depressant effect, with somnolence and dizziness occurring in ≥ 5% of patients. Veozah has a Boxed Warning for hepatotoxicity, with transaminase elevations >3X ULN reported in 2.3% of women in pooled clinical trials. In Linkuet trials, transaminase elevations ≥ 3X ULN occurred in 0.6% of Lynkuet-treated women and 0.4% of placebo-treated women. Both manufacturers recommend monitoring liver function tests during therapy. A major difference in drug-drug interactions stems from different metabolic profiles: Veozah is a CYP1A2 substrate and is contraindicated with CYP1A2 inhibitors, while Lynkuet is primarily metabolized by CYP3A4 and requires dosage modification or avoidance when used with CYP3A4 inhibitors or inducers.
Women suffering from menopause-related VMS now have two nonhormonal options; however, both medications are significantly more expensive than hormone replacement therapy (HRT) and often require prior authorization along with stepped therapy for insurance coverage. A study comparing Veozah or Lynkuet to HRT would be informative.
In their respective phase 3 trials, both agents demonstrated a statistically significant reduction in VMS frequency and severity (≥ hot flashes over 24 hours) compared to placebo. In two 12-week trials, the placebo-subtracted reduction in VMS episodes (baseline ∼ 11 episodes/day) with Veozah was about 2.5 per 24 hours. Similarly, the placebo-subtracted reduction in VMS episodes (baseline ∼ 14 episodes/day) with Lynkuet was about 3.2 per 24 hours in 12-week trials. Notably, across all trials, the placebo group experienced reductions of 4 to 6 episodes per day, suggesting a significant psychological component in VMS improvement. Common side effects for both agents include gastrointestinal issues like abdominal pain and diarrhea, as well as nervous system effects such as insomnia, back pain, and headache. Lynkuet's label notes a central nervous system (CNS) depressant effect, with somnolence and dizziness occurring in ≥ 5% of patients. Veozah has a Boxed Warning for hepatotoxicity, with transaminase elevations >3X ULN reported in 2.3% of women in pooled clinical trials. In Linkuet trials, transaminase elevations ≥ 3X ULN occurred in 0.6% of Lynkuet-treated women and 0.4% of placebo-treated women. Both manufacturers recommend monitoring liver function tests during therapy. A major difference in drug-drug interactions stems from different metabolic profiles: Veozah is a CYP1A2 substrate and is contraindicated with CYP1A2 inhibitors, while Lynkuet is primarily metabolized by CYP3A4 and requires dosage modification or avoidance when used with CYP3A4 inhibitors or inducers.
Women suffering from menopause-related VMS now have two nonhormonal options; however, both medications are significantly more expensive than hormone replacement therapy (HRT) and often require prior authorization along with stepped therapy for insurance coverage. A study comparing Veozah or Lynkuet to HRT would be informative.
