Astellas’ $550 million bet on menopause drug fezolinetant has hit unexpected turbulence. After acing a pair of phase 3 clinical trials and racing to regulators, Astellas has reported the failure of fezolinetant to beat placebo in a late-stage study of patients in Asia.
The study randomized 302 women in China, Korea and Taiwan to take fezolinetant or placebo. After 12 weeks, Astellas saw numerical improvements in the rate of hot flashes from baseline in the fezolinetant arm, but the difference from placebo fell short of statistical significance. Fezolinetant is yet to share data from the study. The one positive is that the 12-week safety data are in line with the results of earlier trials.
It is unclear why the selective neurokinin-3 receptor antagonist fezolinetant failed to beat placebo. Astellas looked to be in a strong position last year when it reported top-line success in the two phase 3 clinical trials designed to support filings for approval in the U.S. and Europe. A long-term safety study forms the other pillar of Astellas’ filing plan in the West.
Like the Asian trial, MOONLIGHT 1, the two earlier phase 3 studies, SKYLIGHT 1 and SKYLIGHT 2, looked at changes in the frequency and severity of moderate to severe vasomotor symptoms, commonly called hot flashes. MOONLIGHT 1 used the lower of the two doses tested in the earlier trials, but that dose beat placebo in SKYLIGHT 1 and SKYLIGHT 2.
The question now is how far the fallout of the failure will reach. Astellas looks to have the data it needs to win approval in the U.S. and Europe, but the failure in Asia could muddy the waters somewhat.
Astellas acquired fezolinetant in its 2017 takeover of Ogeda, which cost it 500 million euros ($550 million) upfront plus a potential 300 million euros in milestones. In 2020, Bayer joined Astellas in the race by paying $425 million upfront to buy KaNDy Therapeutics for neurokinin-1,3 receptor antagonist NT-814. The deal gave Bayer control of a drug that had previously bounced from GlaxoSmithKline to NeRRe Therapeutics to KaNDy.