Last Friday, the US Food and Drug Administration (FDA) approved the first nonhormonal medication to treat hot flashes in menopausal women. The oral therapy (fezolinetant), to be marketed as VEOZAH, is the first nonhormonal neurokinin 3 (NK3) receptor antagonist approved to treat vasomotor symptoms (VMS) due to menopause. It is indicated for patients experiencing moderate to severe symptoms.
The therapy would typically be prescribed for women in their 50s during the menopausal phase estimated to last 7 years, according to Marci English, a vice president of Astellas Pharma, the manufacturer of the medication. Hormonal changes during menopause make the body more sensitive to fluctuations in body temperature, causing VMS such as hot flashes and night sweats.
Significant prevalence, duration, and QOL impact
According to The North American Menopause Society (NAMS), as many as 75% of North American women experience hot flashes during perimenopause, and ~25% of them undergo enough discomfort to seek relief from their clinicians. Most women have hot flashes for 6 months to 2 years, although some data suggest that they last considerably longer—as long as 10 years, depending on when symptoms presented. For a small proportion of women, they may never go away. It is not uncommon for women to experience a recurrence of hot flashes more than 10 years after menopause—even into their 70s or beyond.
Prior to menopause, there is a balance between estrogens and neurokinin B (NKB), a brain chemical. This balance regulates the body’s temperature control center located in the hypothalamus. As women go through menopause, estrogens decline, and this balance is disrupted with the imbalance often leading to VMS. If the hypothalamus senses that a woman is too warm, it starts a chain of events to cool her down. Blood vessels near the surface of the skin begin to dilate, increasing blood flow to the surface in an attempt to dissipate body heat. This produces a red, flushed look to the face and neck in light-skinned women. It may also make a woman perspire to cool the body down. Women may sense their hearts beating faster. A cold chill often follows a hot flash although some women experience only the chill. VEOZAH works by blocking NKB in the hypothalamus resulting in a reduction in the number and intensity of hot flashes.
Menopause-related hot flashes usually follow a consistent pattern unique to each woman, but the pattern differs greatly from woman to woman. Some hot flashes are easily tolerated, some can be annoying or embarrassing, and others can be debilitating.
“Hot flashes as a result of menopause can be a serious physical burden on women and impact their quality of life,” stated Janet Maynard, MD, Director of the Office of Rare Diseases, Pediatrics, Urologic and Reproductive Medicine (ORPURM) within the FDA’s Center for Drug Evaluation and Research (CDER).
Adding potential option to HRT
Hormonal treatments including estrogen and progestin, currently utilized for treating vasomotor symptoms, were linked to elevated risks of blood clots and strokes decades ago, but subsequent clinical studies have shown that the risks are far lower in women in their 40s and 50s.
The approval of VEOZAH, which is a non-hormonal treatment, was based on a late-stage study that showed it helped reduce the frequency and severity of vasomotor symptoms and improved patients’ quality of life over the treatment period.
The medication’s approval is based on results from three Phase 3 clinical trials as part of a development program that collectively enrolled over 3,000 individuals across the US, Canada, and Europe. Results from the SKYLIGHT 1 and SKYLIGHT 2 pivotal trials characterize the efficacy and safety of fezolinetant for the treatment of moderate to severe VMS due to menopause and data from the SKYLIGHT 4 safety study further characterizes the long-term safety profile of fezolinetant. Prior to its approval, use of anti-depressant paroxetine, the selective serotonin-reuptake inhibitor (SSRI), was the only FDA approved non-hormonal option available to patients.
Prescribers: Monitor for 9 months
In the yearlong studies, the drug was found to be effective and generally safe, with side effects including stomach pain, diarrhea, and insomnia, according to the FDA.
Because signs of liver damage emerged in some patients during its clinical trials, the agency said patients should have blood work conducted before initiation of therapy to test for existing liver problems and should then repeat the tests during the first 9 months of taking VEOZAH.
Astellas released a statement indicating that the drug would be priced at $550 for a 30-day supply, not including rebates, and that it would initiate a support program “to help patients access the medication they were prescribed.” The company added that the medication expected to be available in pharmacies within 3 weeks.
The contents of this feature are not provided or reviewed by NPWH.