Hot Flash Drug Succeeds in Two Pivotal Trials

SAN FRANCISCO — Novel agent elinzanetant relieved the frequency and severity of hot flashes in postmenopausal women in two nearly identical phase III trials, OASIS I and OASIS II.

In both trials, the neurokinin-1,3 receptor antagonist significantly reduced the frequency of moderate-to-severe vasomotor symptoms compared with placebo at week 4 (-3.29 and -3.04 hot flashes in OASIS I and II, respectively, both P<0.0001) and week 12 (-3.22 and -3.24, both P<0.0001).

Those reductions exceeded the minimum clinically important reduction of two vasomotor symptoms per day, reported James Simon, MD, of George Washington University and IntimMedicine Specialists in Washington, D.C., who led OASIS I, and JoAnn Pinkerton, MD, of the University of Virginia Health System in Charlottesville, who led OASIS II.

Elinzanetant also reduced the severity of vasomotor symptoms (VMS) at both time points, with reduced sleep disturbance and improved menopause-related quality-of-life at week 12 — all statistically significant compared with placebo in the findings presented at a late-breaking industry session at the American College of Obstetricians and Gynecologists (ACOG) annual meeting.

Simon told MedPage Today that “the results are consistent with the anticipated benefits of this active agent, showing a reduction in hot flashes as early as 1 week, with continued benefit for 4 weeks and 12 weeks, the two primary endpoints mandated by regulators.”

Drug developer Bayer announced in March that it will use these data, along with the 52-week data from the OASIS 3 trial, in a submission to the FDA for marketing authorization.

Pinkerton told MedPage Today that while there are effective hormone therapies for hot flashes, some women can’t take those treatments because of factors like having estrogen-sensitive cancer, blood clots, or stroke.

“Women who have these disruptive hot flushes are very distressed. It affects their workplace productivity and their relationships. … So it’s actually not just a nuisance, these are actually medical issues,” Pinkerton said. “To find that this medication worked quickly and effectively at reducing really severe hot flashes, I think has a big impact for women.”

Headache and fatigue were the most prevalent side effects of elinzanetant. Neither trial found any cases of endometrial hyperplasia, malignant neoplasm, or drug-induced liver injury assessed by a liver safety monitoring board.

For both OASIS I and II, postmenopausal women with moderate to severe vasomotor symptoms (50 hot flashes per week or more) were randomized 1:1 to either 120 mg of elinzanetant for 26 weeks or placebo for 12 weeks then 120 mg of elinzanetant for 14 weeks. OASIS I had 199 women in the elinzanetant group and 197 in the placebo group, while OASIS II had 200 in each group.

Among the secondary endpoints, elinzanetant significantly reduced the severity of vasomotor symptoms at week 4 (-0.33 in OASIS I, P<0.0001 and -0.22 in OASIS II, P=0.0003) and week 12 (-0.40 and -0.29, respectively, P<0.0001). In both trials, elinzanetant additionally reduced the frequency of vasomotor symptoms at week 1 (I and II, respectively: P<0.0001 and P=0.0013), improved sleep disturbances measured by the Patient-Reported Outcomes Measurement Information System Sleep Disturbance Short Form (P<0.0001 for both), and improved menopause-related quality-of-life (P<0.0001 and P=0.0059 on the Menopause Specific Quality of Life Scale) at week 12.

In the previous SWITCH-1 phase II trial led by Simon, researchers found that elinzanetant 120 mg was the optimal dose for relieving VMS symptoms.

In terms of limitations, Pinkerton and Bayer noted that the study populations were mostly white (about 80% in each trial) and young menopausal women, and the study took place during the pandemic, which made enrollment more difficult.

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