Astellas' Menopause Drug Fezolinetant Fails to Outperform Placebo in Asian Phase 3 Trial

Compiled by Fan Dongdong

Recently, fezolinetant, a menopause drug that Astellas invested $550 million in, faced setbacks. In a late-stage trial involving Asian patients, its efficacy failed to outperform that of a placebo.

MOONLIGHT 1 is an ongoing randomized Phase 3 clinical trial. This study enrolled 302 female patients from mainland China, Taiwan, China, and South Korea. Participants were randomly assigned to receive either a 30 mg dose of fezolinetant or a placebo for 24 weeks. The trial employed a double-blind, placebo-controlled design for the first 12 weeks, followed by a 12-week non-controlled extension treatment period.

Trial results showed that after 12 weeks, the hot flash rate in women treated with fezolinetant improved from baseline levels, but the difference compared to the placebo group was not statistically significant. The only positive outcome of the trial was that the safety data for 12 weeks of fezolinetant treatment were consistent with earlier trial results. Notably, just last year, two pivotal Phase 3 trials of fezolinetant had achieved positive results.

It is currently unclear why fezolinetant failed to outperform placebo in the Asian trial. Similar to the MOONLIGHT 1 Asian trial, the two previously successful Phase 3 studies, SKYLIGHT 1 and SKYLIGHT 2, also examined changes in the frequency and severity of moderate to severe vasomotor symptoms (commonly referred to as hot flashes) in menopausal women.

In 2017, Astellas announced the completion of a $550 million acquisition of Ogeda, a Belgian biotechnology company, through which Astellas obtained fezolinetant. Fezolinetant, a non-hormonal therapy, is an orally administered, non-hormonal selective neurokinin-3 receptor (NK3R) antagonist that can normalize KNDy neuron activity by blocking neurokinin B (NKB) signaling, thereby regulating the body's temperature control center and reducing the frequency and severity of hot flashes.

For now, the regulatory challenge Astellas needs to face is how long the impact of this trial failure will last. Previously, with positive results from the SKYLIGHT 1 and SKYLIGHT 2 studies as well as the long-term safety study SKYLIGHT 4, Astellas seemed to have secured entry into the U.S. and European markets, but the painful failure of the Asian trial could somewhat disrupt this situation.

Reference Source:

1、Astellas' menopause drug suffers rare setback as failed Asian trial blots previously pristine record

2、Astellas: Phase 3 Study Of Fezolinetant On VMS Associated With Menopause Did Not Show Efficacy