Fezolinetant Benefits Women Not Suited for Hormone Therapy

PHILADELPHIA — Fezolinetant (Veozah) improved menopause-related vasomotor symptoms in women unsuited or unwilling to take hormone therapy, according to a pooled analysis of two phase III studies.

The analysis of the SKYLIGHT-1 and -2 trials showed significant improvements with two different dosages of the newly approved drug versus placebo in both the frequency and severity of moderate-to-severe vasomotor symptoms from baseline to week 12:

• Frequency 30 mg: least squares mean difference -2.15 (95% CI -2.84 to -1.45)
• Frequency 45 mg: least squares mean difference -2.51 (95% CI -3.20 to -1.82)
• Severity 30 mg: least squares mean difference -0.20 (95% CI -0.31 to -0.08)
• Severity 45 mg: least squares mean difference -0.24 (95% CI -0.35 to -0.13)

Similar results were seen across all subgroups of women with various hormone therapy histories, reported Nanette Santoro, MD, of the University of Colorado School of Medicine in Aurora, during the annual meeting of the Menopause Society.

Earlier this year, the FDA approved fezolinetant for the treatment of moderate-to-severe hot flashes. Unlike hormonal treatments, this first-in-class drug works by blocking neurokinin 3 (NK3) receptors, which help regulate body temperature.

“I have been very interested in that element of the NK3 receptor antagonists just because of the science behind it, and the fact that a treatment that is not hormonal has the potential to bypass estrogen and be as effective for hot flashes as estrogen is, which is extremely attractive and badly needed in clinical practice,” Santoro said during her presentation.

She told MedPage Today in an interview in which a communications representative from drugmaker Astellas was also present, that when she poured through the pooled data, she was curious about the experiences of women who either can’t or won’t take hormones, including those who are hormone aversive: “Did they get the same relief? What’s the magnitude of relief that they get with desolate attempts? Is it similar to the larger group?”

It turns out that the answer to all three of those questions is yes, with the study authors noting that “the findings are consistent with the effect observed in the overall participant population.”

The drug also helped with sleep, which Santoro said is an added bonus. She detailed how, irrespective of hormone therapy history, sleep disturbance improved by week 12 compared with placebo in both fezolinetant groups. Improvements were greater for the 45-mg group, which is the dose that was ultimately approved by the FDA, with exceptions for the contraindicated and naive/willing subgroups.

Treatment-emergent adverse events (TEAEs) occurred in 41.3% of the placebo group, 40.8% of the 30 mg-group, and 39.4% of the 45-mg group. The most common TEAE was headache, which occurred in 5.5%, 4.2%, and 5.6%, respectively. One serious drug-related TEAE occurred in the fezolinetant 30 mg group.

“It looks like we have kind of a very specific bullet for hot flashes and it gives us a new pathway,” Santoro said, adding that fezolinetant is “a godsend to my patients who cannot take hormone therapy.”

The SKYLIGHT-2 trial was a double-blind, placebo-controlled, phase III study that included 501 women ages 40 to 65 (mean age 54.3) with moderate-to-severe vasomotor symptoms, with a minimum average of ≥7 hot flashes each day. Over 12 weeks, participants were given placebo, fezolinetant 30 mg, or fezolinetant 45 mg once a day. At baseline, participants answered a questionnaire, which included questions about hormone therapy history.

Significant improvements in vasomotor symptom frequency and severity were seen through the first 12 weeks of treatment in both dose groups compared with the placebo group.

For this analysis, participants were broken into mutually exclusive subgroup categories based on the hormone therapy questionnaire, including contraindicated, caution, stopped for medical concerns, averse, naive/willing.

In total, 1,022 participants were included in the pooled data group, with 342 in the placebo group, 339 in the 30-mg group, and 341 in the 45-mg group.

After Santoro’s presentation, an audience member asked about women with breast cancer. Santoro said that while cancer patients weren’t included in the SKYLIGHT trials, she prescribes the drug to her own patients who have breast cancer, and she’s been pleased with the results.

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