Astellas Announces Positive Phase 3 Results for Fezolinetant in Treatment of Moderate to Severe Menopausal Vasomotor Symptoms

Compiled by Fan Dongdong

Astellas Pharma Announces Positive Results from Two Pivotal Phase 3 Trials of Fezolinetant, an Oral Non-Hormonal Therapy for Moderate to Severe Vasomotor Symptoms (VMS) Associated with Menopause

SKYLIGHT 1 and SKYLIGHT 2 were double-blind, placebo-controlled studies that collectively enrolled 1,028 female patients with moderate to severe vasomotor symptoms across 307 sites in countries and regions including the United States, Canada, and Europe. Both trials featured an initial 12-week double-blind, placebo-controlled phase, followed by a 40-week active-treatment extension period.

Trial results demonstrated that both pivotal studies met all four primary co-primary endpoints. Compared with the placebo group, female subjects receiving daily doses of 30 mg and 45 mg fezolinetant achieved statistically significant reductions in both the frequency and severity of moderate-to-severe vasomotor symptoms (VMS) from baseline to Week 4 and Week 12.

In the trials, no more than 2% of subjects experienced serious treatment-emergent adverse events (TEAEs), with headache being the most commonly reported adverse reaction. The SKYLIGHT 1 and SKYLIGHT 2 studies are currently ongoing, with patients scheduled to complete a total of 52 weeks of treatment and follow-up. Following analysis of the efficacy data at 52 weeks, detailed results from both trials will be submitted for publication and presented at relevant medical conferences.

Fezolinetant, a non-hormonal therapy, is an oral, non-hormonal, selective neurokinin-3 receptor (NK3R) antagonist. By blocking neurokinin B (NKB) signaling, this drug normalizes KNDy neuron activity, thereby modulating the thermoregulatory center and reducing the frequency and severity of hot flashes. In 2017, Astellas announced the completion of its €800 million acquisition of Ogeda, a Belgian biotechnology company, through which it acquired fezolinetant.

This transaction was driven by the results of a Phase IIa clinical study of the drug, in which fezolinetant reduced hot flashes—the most common symptom of menopause-related vasomotor symptoms—by 93% after 12 weeks of treatment, compared with a 54% reduction in the placebo group. Furthermore, at the same time point, fezolinetant reduced the severity of hot flashes by 70%, versus a 23% reduction in the placebo group.

Vasomotor symptoms, such as menopause-related hot flashes and night sweats, are common among menopausal women. It is estimated that approximately 57% of women aged 40 to 64 worldwide experience these symptoms, which often lead to anxiety, irritability, reduced work productivity, and depression, significantly impacting sleep and quality of life.

Hormone therapy is currently the first-line treatment for women with vasomotor symptoms who have no contraindications. However, due to the long-term adverse effects associated with hormone therapy, its use requires a careful balance between safety and efficacy, creating an urgent clinical need for the development of corresponding non-hormonal therapies. If approved by regulatory authorities in the future, oral fezolinetant will become a first-in-class non-hormonal treatment option.

In addition to the two aforementioned trials, Astellas is also conducting another trial, SKYLIGHT 4 (NCT04003389), a 52-week double-blind, placebo-controlled study designed to evaluate the long-term safety of fezolinetant. This trial enrolled 1,833 eligible female participants across 216 sites in the United States, Canada, and Europe.

Notably, in January last year, Astellas’ fezolinetant received clinical approval in China for the treatment of moderate to severe vasomotor symptoms (VMS).

Reference Sources:

1.Astellas scores a pair of trial wins for menopausal hot flash med, raising the pitch of looming Bayer standoff

2.Astellas Announces Positive Topline Results from Two Phase 3 Pivotal Global Trials of Fezolinetant for the Nonhormonal Treatment of Vasomotor Symptoms in Postmenopausal Women