Astellas Pharma Inc.'s nonhormonal compound fezolinetant reduced vasomotor symptoms in postmenopausal women in a mid-stage study.
The phase 2b trial results, announced at the Endocrine Society's Annual Meeting in New Orleans, met the U.S. Food and Drug Administration's four recommended goals of producing a mean decrease in frequency and severity of vasomotor symptoms, which include hot flashes and night sweats, after four weeks and 12 weeks.
Fezolinetant blocks neurokinin B signaling and normalizes neuron activity that modulates the temperature control center.
The study tested oral fezolinetant against placebo in 356 women, with doses ranging from 15 milligrams to 90 milligrams twice daily or 30 milligrams to 120 milligrams once daily. Most groups in the trial showed statistically significant mean changes in frequency and severity of the symptoms from placebo, the Tokyo-based company said in its March 26 press release.
Across the 12-week treatment period, the reduction in symptoms was maintained, and symptoms returned to their original frequency and severity once treatment was stopped.
The placebo treatment showed a 55% reduction in symptoms compared to the twice-daily fezolinetant dose showing a 74.3% to 86.9% reduction and the once-daily fezolinetant showing 75.1% to 77.9% reduction. The severity of symptoms also showed improvement in both fezolinetant doses compared to placebo, Astellas reported.
Adverse events were similar across tested groups, and no deaths or treatment-related serious adverse events were reported.
Common side effects included headache, nausea, urinary tract infection, diarrhea and upper respiratory tract infections. However, nine patients who received the higher fezolinetant dose regimens experienced increases in certain liver enzymes associated with liver damage or injury. The enzyme levels returned to baseline when patients discontinued the treatment, Astellas said.
About 57% of women between 40 and 64 years experience hot flashes and sweating, which can "significantly impact a woman's quality of life," the study's lead investigator Arthur Waldbaum said. According to Waldbaum, limited nonhormonal therapies exist for such symptoms, which are among the most common in menopause.