European regulators have backed the approval of Lynkuet (elinzanetant, Bayer AG) for treating moderate-to-severe vasomotor symptoms (VMS). The drug targets hot flushes (also known as hot flashes) linked to menopause and those triggered by adjuvant endocrine therapy (AET) for breast cancer. 

VMS can stem from various causes, including natural menopause or medical treatments such as those for breast cancer. VMS affects up to 80% of women during the menopausal transition, with more than one third experiencing severe symptoms that can persist for more than a decade, significantly impacting quality of life. The condition affects women typically in their 40s or early 50s and are usually related to the progressive decline of ovarian function; medical interventions can trigger similar symptoms in younger populations.

Lynkuet offers a novel therapeutic approach to menopausal VMS by selectively blocking NK-1 and NK-3 receptors on hypothalamic KNDy neurons. These neurons, involved in thermoregulation, become hyperactive due to declining estrogen levels (such as during menopause or AET), leading to increased neurokinin B and substance P signaling. Elinzanetant, the active substance in Lynkuet, is postulated to reduce this hyperactivity, helping to restore thermoregulatory balance and alleviate symptoms such as hot flushes and sleep disturbances associated with menopause.

During its September meeting, the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use noted that the main benefit of Lynkuet was the reduction in frequency of moderate-to-severe VMS. Four phase 3 trials — OASIS 1, 2, 3, and 4 — have assessed the safety and efficacy of elinzanetant. 

In OASIS 1 and 2, postmenopausal women aged 40-65 experienced significant reductions in VMS frequency and severity compared with placebo at weeks 4 and 12, with more than 80% of elinzanetant-treated participants achieving at least a 50% reduction in VMS frequency by week 26. Both trials also met key secondary endpoints, including early symptom improvement by week 1, better sleep, and enhanced quality of life. OASIS 3 confirmed the durability of effect over 52 weeks, reinforcing earlier findings and reporting a favorable safety profile.

In OASIS 4, which focused on women undergoing endocrine therapy for hormone receptor-positive breast cancer, elinzanetant significantly reduced VMS frequency at weeks 4 and 12 and improved sleep and quality of life. 

The most frequently reported side effects of Lynkuet across both approved indications include fatigue, drowsiness, headache, diarrhea, and muscle spasms. In women experiencing AET-associated VMS, depression was also observed as a side effect. Lynkuet is contraindicated during pregnancy.

Lynkuet will be available as 60-mg soft capsules, is classified as a gynecologic product, and is intended for once-daily oral administration. 

Detailed recommendations for Lynkuet use will be described in the summary of product characteristics, which will be published on the EMA website after the European Commission grants marketing authorization.