Fezolinetant for treatment of moderate-to-severe vasomotor symptoms associated with menopause (SKYLIGHT 1): a phase 3 randomised controlled study

Lederman, Samuel; Ottery, Faith D; Cano, Antonio; Santoro, Nanette; Shapiro, Marla; Stute, Petra; Thurston, Rebecca C.; English, Marci; Franklin, Catherine; Lee, Misun

doi:10.1016/s0140-6736(23)00085-5

Cited by 108 publications

(164 citation statements)

References 28 publications

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“…A third agent, antagonist (MLE4901), 117,118,121 is no longer being pursued as a VMS treatment. Published trial results include demonstration of efficacy of fezolinetant 116,119,120 and elinzanetant 116,121 relative to placebo. Fezolinetant is a selective neurokinin B receptor-3 antagonist found to be more beneficial than placebo within and up to 12 weeks of use.…”

Section: Neurokinin B Antagonistsmentioning

confidence: 99%

“…Phase 3 trials have demonstrated safety, with headache as the most common AE. 120 Elevation of hepatic enzymes was rare and resolved either during continued treatment or with treatment discontinuation.…”

Section: Neurokinin B Antagonistsmentioning

confidence: 99%

“…Elinzanetant is a dual neurokinin B receptor-3 and receptor-1 antagonist found to be more beneficial than placebo within 2 weeks of use. Phase 3 trials have demonstrated safety, with headache as the most common AE 120 . Elevation of hepatic enzymes was rare and resolved either during continued treatment or with treatment discontinuation.…”

Section: Prescription Therapiesmentioning

confidence: 99%

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The 2023 nonhormone therapy position statement of The North American Menopause Society

2023

Menopause

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Objective To update the evidence-based Nonhormonal Management of Menopause-Associated Vasomotor Symptoms: 2015 Position Statement of The North American Menopause Society. Methods An advisory panel of clinicians and research experts in women’s health were selected to review and evaluate the literature published since the Nonhormonal Management of Menopause-Associated Vasomotor Symptoms: 2015 Position Statement of The North American Menopause Society. Topics were divided into five sections for ease of review: lifestyle; mind-body techniques; prescription therapies; dietary supplements; and acupuncture, other treatments, and technologies. The panel assessed the most current and available literature to determine whether to recommend or not recommend use based on these levels of evidence: Level I, good and consistent scientific evidence; Level II, limited or inconsistent scientific evidence, and Level III, consensus and expert opinion. Results Evidence-based review of the literature resulted in several nonhormone options for the treatment of vasomotor symptoms. Recommended: Cognitive-behavioral therapy, clinical hypnosis, selective serotonin reuptake inhibitors/serotonin-norepinephrine reuptake inhibitors, gabapentin, fezolinetant (Level I); oxybutynin (Levels I-II); weight loss, stellate ganglion block (Levels II-III). Not recommended: Paced respiration (Level I); supplements/herbal remedies (Levels I-II); cooling techniques, avoiding triggers, exercise, yoga, mindfulness-based intervention, relaxation, suvorexant, soy foods and soy extracts, soy metabolite equol, cannabinoids, acupuncture, calibration of neural oscillations (Level II); chiropractic interventions, clonidine; (Levels I-III); dietary modification and pregabalin (Level III). Conclusion Hormone therapy remains the most effective treatment for vasomotor symptoms and should be considered in menopausal women within 10 years of their final menstrual periods. For women who are not good candidates for hormone therapy because of contraindications (eg, estrogen-dependent cancers or cardiovascular disease) or personal preference, it is important for healthcare professionals to be well informed about nonhormone treatment options for reducing vasomotor symptoms that are supported by the evidence.

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Section: Neurokinin B Antagonistsmentioning

confidence: 99%

Section: Neurokinin B Antagonistsmentioning

confidence: 99%

Section: Prescription Therapiesmentioning

confidence: 99%

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The 2023 nonhormone therapy position statement of The North American Menopause Society

2023

Menopause

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“…This NK3R antagonist differs slightly from elinzanetant, an NK1,3R dual antagonist, nearing completion of phase 3 trials. 4 Trials on the efficacy and safety of oral fezolinetant 45 mg showed reduction in daily frequency of moderate to severe vasomotor symptoms beyond that of placebo by -2.55 (SE, 0.43 [P < .001]) 5 and -2.53 (SE, 0.55 [P < .001]). 6 Furthermore, significant improvement in frequency and severity of moderate to severe vasomotor symptoms was rapid, observed as early as 1 week after treatment onset, and was sustained through week 52 in an open-label trial extension.…”

Section: Novel Nonhormonal Therapiesmentioning

confidence: 99%

“…7 Among those taking menopausal hormone therapy, the proportion with at least a 50% reduction in vasomotor symptom frequency was 73% vs 58% with placebo (difference, 15%); whereas among those taking fezolinetant, the proportion was 57% vs 30% with placebo (difference, 27%). 5 NKB antagonists are a salutary breakthrough for those unable or choosing not to take menopausal hormone therapy. Breast cancer survivors have tremendous vasomotor symptom burden; cancer treatments result in early menopause and severe symptoms that can last for years.…”

Section: Novel Nonhormonal Therapiesmentioning

confidence: 99%

Nonhormonal Therapies for Menopausal Vasomotor Symptoms

Christ,

Navarro,

Reed

2023

JAMA

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Elinzanetant for the Treatment of Vasomotor Symptoms Associated With Menopause

Pinkerton,

Simon,

Joffe

et al. 2024

JAMA

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ImportanceSafe and effective nonhormonal treatments for menopausal vasomotor symptoms (VMS) are needed.ObjectiveTo evaluate the efficacy and safety of elinzanetant, a selective neurokinin-1,3 receptor antagonist, for the treatment of moderate to severe menopausal vasomotor symptoms.Design, Setting, and ParticipantsTwo randomized double-blind phase 3 trials (OASIS 1 and 2) included postmenopausal participants aged 40 to 65 years experiencing moderate to severe vasomotor symptoms (OASIS 1: 77 sites in the US, Europe, and Israel from August 27, 2021, to November 27, 2023, and OASIS 2: 77 sites in the US, Canada, and Europe from October 29, 2021, to October 10, 2023).InterventionOnce daily oral elinzanetant, 120 mg, for 26 weeks or matching placebo for 12 weeks followed by elinzanetant, 120 mg, for 14 weeks.Main Outcomes and MeasuresPrimary end points included mean change in frequency and severity of moderate to severe vasomotor symptoms from baseline to weeks 4 and 12, measured by the electronic hot flash daily diary. Secondary end points included Patient-Reported Outcomes Measurement Information System Sleep Disturbance Short Form 8b total T score and Menopause-Specific Quality of Life questionnaire total score from baseline to week 12.ResultsEligible participants (mean [SD] age, OASIS 1: 54.6 [4.9] years; OASIS 2: 54.6 [4.8] years) were randomized to elinzanetant (OASIS 1: n = 199; OASIS 2: n = 200) or placebo (OASIS 1: n = 197; OASIS 2: n = 200). A total of 309 (78.0%) and 324 (81.0%) completed OASIS 1 and 2, respectively. For the elinzanetant and placebo groups, the baseline mean (SD) VMS per 24 hours were 13.4 (6.6) vs 14.3 (13.9) (OASIS 1) and 14.7 (11.1) v 16.2 (11.2) (OASIS 2). Baseline VMS severity was 2.6 (0.2) vs 2.5 (0.2) (OASIS 1) and 2.5 (0.2) vs 2.5 (0.2) (OASIS 2). Elinzanetant significantly reduced VMS frequency at week 4 (OASIS 1: −3.3 [95% CI, −4.5 to −2.1], P &lt; .001; OASIS 2: −3.0 [95% CI, −4.4 to −1.7], P &lt; .001) and at week 12 (OASIS 1: −3.2 [95% CI, −4.8 to −1.6], P &lt; .001; OASIS 2: −3.2 [95% CI, −4.6 to −1.9], P &lt; .001). Elinzanetant also improved VMS severity at week 4 (OASIS 1: −0.3 [95% CI, −0.4 to −0.2], P &lt; .001; OASIS 2: −0.2 [95 CI, −0.3 to −0.1], P &lt; .001) and week 12 (OASIS 1: −0.4 [95% CI, −0.5 to −0.3], P &lt; .001; OASIS 2: −0.3 [95% CI, −0.4 to −0.1], P &lt; .001). Elinzanetant improved sleep disturbances and menopause-related quality of life at week 12, and the safety profile was favorable.Conclusions and RelevanceElinzanetant was well tolerated and efficacious for moderate to severe menopausal VMS.Trial RegistrationClinicalTrials.gov Identifier: OASIS 1: NCT05042362, OASIS 2: NCT05099159

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Fezolinetant for treatment of moderate-to-severe vasomotor symptoms associated with menopause (SKYLIGHT 1): a phase 3 randomised controlled study

Cited by 108 publications

References 28 publications

The 2023 nonhormone therapy position statement of The North American Menopause Society

The 2023 nonhormone therapy position statement of The North American Menopause Society

Nonhormonal Therapies for Menopausal Vasomotor Symptoms

Elinzanetant for the Treatment of Vasomotor Symptoms Associated With Menopause

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