Long-term data supports non-hormonal drug for the treatment of hot flashes

CHICAGO – The non-hormonal drug elinzanetant reduced the frequency of moderate to severe hot flashes in postmenopausal women and appeared to have a favorable safety profile, according to data from the long-term OASIS 3 study.

Women with moderate to severe vasomotor symptoms (VMS) treated with elinzanetant for 12 weeks had an average of 1.6 hot flashes per day compared to 3.4 per day with placebo (mean difference between elinzanetant and placebo from baseline -1.6, 95% CI -2.0 to -1.1, PAnnual meeting of the Menopause Society.

This is consistent with previous results from OASIS 1 and 2, which showed significant reductions in VMS frequency at weeks 4 and 12 compared with placebo. The reduction was maintained through week 50, Simon said. Safety assessments at week 52 showed no cases of Hy's Law (a measure of drug-induced liver injury) and no evidence of cholestatic damage.

“This is a new, very promising treatment for hot flashes – non-hormonal – that remains effective for 52 weeks and appears to have very little, if any, effect on the liver,” Simon said. MedPage Today“This is historic.”

In addition, safety assessments revealed no cases of endometrial hyperplasia or malignant neoplasms, no evidence of liver toxicity, and changes in bone mineral density consistent with expected age-related loss.

Elinzanetant is an experimental dual neurokinin 1 and 3 receptor antagonist (NK-1 and 3) under review by the FDA for the treatment of moderate to severe VMS associated with menopause (the developer filed a New Drug Application in August). NK-3 may be involved in the impaired thermoregulation associated with estrogen decline during menopause, and NK-1 may play a role in sleep and peripheral vasodilation. Fezolinetant (Veozah), an approved drug in the same category, recently had a label update requiring liver blood testing after the agency received a postmarketing report of liver injury.

Non-hormonal options may be a good option for women whose menopausal symptoms are not being treated or for whom hormone therapy is contraindicated, wrote Stephanie Faubion MD, MBA, of the Mayo Clinic in Jacksonville, Florida, and her colleague in a JAMA Editorial on the results of OASIS 1 and 2.

“It is important to note that menopausal symptoms such as VMS rarely occur in isolation, but often occur together in symptom clusters,” Faubion explained. “Therefore, medications that can treat multiple symptoms associated with menopause are more attractive than requiring multiple treatments to separately treat, for example, VMS, sleep and mood disturbances, weight gain, and brain fog.”

The OASIS 3 study included 628 naturally or surgically conceived postmenopausal women with moderate to severe VMS. They were randomized to receive either 120 mg of elinzanetant or placebo orally once daily. The average age was about 55 years, about 80% of the women were white, and the average frequency of VMS was about seven per day. Participants documented VMS in a diary.

Secondary patient-reported outcomes (PROs) included mean change from baseline in sleep disturbances, measured by the Patient-Reported Outcomes Measurement Information System Sleep Disturbance Short Form (PROMIS SD SF) 8b total T-score, and in quality of life, measured by the Menopause-Specific Quality of Life (MENQOL) total score.

For PROMIS SD SF 8b, mean changes from baseline to week 52 were -9.4 and -5.7 for the elinzanetant and placebo groups, respectively, from baseline means of 57.4 and 58. For MENQOL, mean changes were -1.3 and -1.1 for elinzanetant versus placebo, from baseline means of 4.1 and 4.4.

Of the women in the elinzanetant and placebo groups, 70% and 61.1%, respectively, experienced at least one treatment-emergent adverse event (TEAE). The most common TEAEs occurring in more than 5% of participants in each treatment group were headache, COVID-19, and fatigue. In the treatment and placebo groups, 4.2% and 1.9% of participants, respectively, had serious TEAEs. Investigators did not consider any TEAEs to be treatment-emergent.

Limitations of the study included the predominantly white patient population and the use of PROs. The study did not include perimenopausal women or those with VMS due to endocrine therapy for breast cancer. OASIS 4 will evaluate the safety and efficacy of elinzanetant in patients undergoing cancer therapy and at high risk for breast cancer.