At baseline, the LH:FSH ratio was about 3. “With treatment, that ratio normalized to about 1, which is where it is in healthy women,” he said. The decrease in LH:FSH ratio occurred in a dose-dependent fashion and was statistically significant (P less than .001 for 180 mg fezolinetant versus placebo).
Dr. Fraser and his collaborators also tracked anti-müllerian hormone (AMH) levels, ovarian volume, and number of follicles. Although the investigators saw trends toward reduction in AMH levels and toward smaller ovarian volumes, these trends weren’t significant. “It was somewhat ambitious, I guess, to consider we’d hit these endpoints within 12 weeks,” he said. There were no serious drug-related adverse events.
“Most importantly, I would say, we did not get an increase in menses frequency, and, of course, that’s an important marker for fertility,” said Dr. Fraser. “There’s a debate in PCOS about whether this disease is driven by a malfunction in the brain or a malfunction in the ovaries. I guess on face value, perhaps this problem is in the ovaries.”
With the trends toward lower AMH and ovarian volumes, the research team is left wondering what would happen if the duration of therapy were extended. “Perhaps, the system would have been reset, and the frequency would have been restored. … So one thought that we have is to prolong the study in future trials and see if that could lead to an increase in fertility in PCOS,” said Dr. Fraser.
Fezolinetant is also being studied for menopause-related hot flashes in the United States and Europe.
Dr. Fraser is an employee of Ogeda, which sponsored the trial. Ogeda is a wholly owned subsidiary of Astelas.
SOURCE: Fraser G et al. ENDO 2018, Abstract SAT-305-LB.