New Medication for Hot Flushes

The neurokinin-3 receptor antagonist, fezolinetant, is now available for the treatment of moderate to severe vasomotor symptoms (VMS) associated with menopause. This is the first non-hormonal medication approved for this indication.

The physiology of VMS is not fully understood. However, signalling via the kisspeptin/neurokinin B/dynorphin (KNDy) neurons is thought to be involved. These neurons innervate the thermoregulatory centre of the hypothalamus and are normally inhibited by estrogen and stimulated by neurokinin B. As estrogen levels decline during menopause, neurokinin B signalling increases activity at the thermoregulatory centre, which can lead to VMS. Fezolinetant blocks neurokinin B signalling, thereby normalising KNDy neuronal activity and reducing VMS.

The SKYLIGHT 2 trial investigated the efficacy of fezolinetant in reducing the frequency and severity of VMS. At week 12, the mean change in VMS frequency was -51.60% for fezolinetant 30mg, 55.16% for fezolinetant 45mg, and -33.60% for placebo. The reduction in VMS frequency compared to placebo was statistically significant in both fezolinetant dose groups at all time points between weeks 1 and 12. While there are currently no head-to-head studies comparing fezolinetant with estrogen, a recent meta-analysis suggests that its efficacy may be similar to that of hormonal therapies and greater than that of available non-hormonal therapies.

Fezolinetant is supplied as an oral tablet for daily administration. Serious treatment-emergent adverse effects were infrequently reported in clinical trials. Some elevations in liver enzymes occurred. These were generally asymptomatic and returned to baseline with continuing treatment or discontinuation. Fezolinetant is a substrate of CYP1A2, and the concomitant use of moderate or strong CYP1A2 inducers is contraindicated.

Fezolinetant may be an appropriate alternative for the treatment of VMS in women who cannot take hormonal therapies or for whom estrogen therapies are not effective.