Veozah (fezolinetant) / Astellas - LARVOL DELTA

A profile of safety and efficacy of fezolinetant for the treatment of menopausal vasomotor symptoms. (PubMed, Expert Rev Clin Pharmacol) - "Fezolinetant represents a highly anticipated innovation, offering the possibility to bridge the therapeutic gap for many women who cannot or do not wish to use MHT. While the potential application of fezolinetant in some clinical settings will add substantial value to the management of VMS, some research gaps need to be addressed in order to provide meaningful insight into the benefit-risk profile that ultimately will improve counseling and prescription tailoring in symptomatic menopausal women."

Journal • Review • CNS Disorders • Sleep Disorder

The Role of Patient-Reported Outcomes in US FDA Novel Drug Approvals and Reimbursement Decisions (2020-2024) (ISPOR 2025) - "Rinvoq (AbbVie) - PRO data showed improved quality of life in rheumatoid arthritis, contributing to $2.3 billion...Zeposia (Bristol-Myers Squibb) - PROs on fatigue reduction generated $500 million. Imcivree (Rhythm Pharmaceuticals) - PRO data supported FDA approval 2022: FDA : 37 drugs, with 30% (11 drugs) Reimbursement : 85 total approvals, with 35% (30 approvals) Adbry (LEO Pharma) - PROs on itch reduction generated $90 million . Camzyos (Bristol-Myers Squibb) - Symptom relief PROs were key 2023: FDA : 49 drugs, with 33% (16 drugs) Reimbursement 95 total approvals, with 45% (43 approvals. Leqembi (Eisai/Biogen) - FDA approval and Medicare conditional reimbursement for Alzheimer's disease leveraged PROs on cognitive function improvements, generating $200 million/ Jaypirca (Eli Lilly) - Patient-reported symptom relief supported FDA and payer decisions for mantle cell lymphoma... The inclusion of PROs in FDA novel drug approvals increased from 18% in 2020 to 40% in..."

Clinical • Patient reported outcomes • Reimbursement • US reimbursement • Alzheimer's Disease • CNS Disorders • Fatigue • Hematological Malignancies • Immunology • Infectious Disease • Inflammatory Arthritis • Lymphoma • Mantle Cell Lymphoma • Oncology • Rheumatoid Arthritis • Rheumatology

Physiologically Based Pharmacokinetic (PBPK) Model to Predict the Magnitude of Drug-Drug Interaction Between Fezolinetant and CYP1A2 Inhibitors. (PubMed, J Clin Pharmacol) - "Fezolinetant is primarily metabolized by CYP1A2 and was found to be a sensitive substrate for CYP1A2 metabolism based on a clinical DDI study with strong CYP1A2 inhibitor, fluvoxamine...The final verified model was used to predict fezolinetant exposure following coadministration with mexiletine (moderate CYP1A2 inhibitor), ciprofloxacin (moderate CYP1A2 inhibitor), and cimetidine (weak CYP1A2 inhibitor)...Another moderate CYP1A2 inhibitor, ciprofloxacin, was predicted to increase fezolinetant Cmax by 1.39 to 1.49 fold and AUCinf by and 1.99 to 2.33 fold. The results of the PBPK analysis supported global labeling language statements for fezolinetant."

Journal • PK/PD data • Women's Health • CYP1A2

FLASH-Breast: Evaluating the Efficacy of Fezolinetant in Reducing Vasomotor Symptoms in Women With Breast Cancer on Endocrine Therapy (clinicaltrials.gov) - P2 | N=92 | Not yet recruiting | Sponsor: Yale University

New P2 trial • Breast Cancer • Oncology • Solid Tumor

An Open-Label, Single and Multiple Dose Study to Evaluate the Pharmacokinetics and Safety of Fezolinetant in Healthy Chinese Female Subjects. (PubMed, Drug Des Devel Ther) - "In total, 3 (18.8%) subjects experienced 4 drug-related treatment-emergent adverse events; all mild in severity. Linear PK was confirmed within the dose range of 15 to 60 mg in healthy Chinese women."

Journal • PK/PD data

In menopause-related moderate-to-severe vasomotor symptoms not suitable for hormone therapy, fezolinetant safely improved symptoms. (PubMed, Ann Intern Med) - "GIM/FP/GP: [Formula: see text]."

Journal

Evaluation of the Impact of Fezolinetant vs Placebo on Indirect Costs Among Women With VMS Associated With Menopause (ISPOR 2025) - P3 | "Fezolinetant, which alleviates VMS frequency and severity, offers meaningful work productivity benefits and reduced indirect costs for women with moderate to severe VMS, underscoring a potential economic value in managing menopause-related symptoms."

Clinical • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Fatigue • Mood Disorders • Psychiatry • Sleep Disorder

A New Hope for Woman with Vasomotor Symptoms: Neurokinin B Antagonists. (PubMed, J Clin Med) - "In 2023, the FDA approved fezolinetant, the first selective NK3R antagonist, for the treatment of moderate to severe VMS associated with menopause. In this regard, elinzanetant represents a promising non-hormonal treatment that targets the underlying causes of VMS through NK-1 and NK-3 receptor pathways. The development of neurokinin B antagonist for VMS treatment exemplifies the impact of advanced pharmacological research on gynecological endocrinology."

Journal • Review • CNS Disorders • Endocrine Disorders • Sleep Disorder

Starlight 3: A Study to Assess Long-term Safety of Fezolinetant Given to Japanese Women Going Through Menopause (clinicaltrials.gov) - P3 | N=277 | Active, not recruiting | Sponsor: Astellas Pharma Inc | Recruiting ➔ Active, not recruiting

Enrollment closed

Menopause part I: Vasomotor symptoms (I). (PubMed, Taiwan J Obstet Gynecol) - "By contrast, another MONGLIGHT RCTs for East Asia population seemed to controversial therapeutic effect for VMS treatment, but there is no doubt that safety issue is also satisfied, contributing to the need of more RCTs to validate its efficacy in diverse population. The current review will summary the recent advance of this new landscape in the management of women with moderate-to-severe VMS and particularly focus on the fezolinetant product."

Clinical • Journal • Review

Nonhormonal Treatment of Vasomotor Symptoms of Menopause. (PubMed, Cardiol Rev) - "Various nonhormonal options, including lifestyle modifications, acupuncture, cognitive behavioral therapy, and pharmacological agents such as SSRIs/SNRIs, gabapentin, clonidine, and the emerging class of neurokinin-3 receptor antagonists, are examined. Clinical trials demonstrate that SSRIs (eg, paroxetine) and SNRIs (eg, venlafaxine) provide significant VMS relief, particularly for women who are unable to use HRT. Neurokinin-3 receptor antagonists, such as fezolinetant, show promising results in reducing hot flashes without affecting cardiovascular health. While more research is needed to further assess long-term outcomes, nonhormonal therapies present a viable and safer alternative for managing VMS, especially for women at risk for cardiovascular complications."

Journal • Breast Cancer • Cardiovascular • Oncology • Solid Tumor

Fezolinetant effect on vasomotor symptoms due to menopause in women unsuitable for hormone therapy. (PubMed, Curr Med Res Opin) - P3 | "This pooled analysis demonstrated efficacy of fezolinetant vs. placebo in reducing frequency and severity of VMS due to menopause in participants unsuitable for HT. SKYLIGHT 1 - ClinicalTrials.gov, NCT04003155; https://clinicaltrials.gov/ct2/show/NCT04003155 (conducted between July 2019 and August 2021); SKYLIGHT 2 - ClinicalTrials.gov, NCT04003142; https://clinicaltrials.gov/ct2/show/NCT04003142 (conducted between July 2019 and April 2021)."

Journal • CNS Disorders • Sleep Disorder

Management of vasomotor symptoms in cancer patients. (PubMed, Oncologist) - "The evidence for various treatment options, including novel agents such as fezolinetant that target the hypothalamic thermoregulatory pathway, will be evaluated. Finally, special considerations in different patient populations based on cancer types (eg, breast, prostate) and age groups (eg, older adults) will be explored."

Journal • Review • Breast Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

A Study to Confirm if Fezolinetant Helps Reduce Hot Flashes in Chinese Women Going Through Menopause (clinicaltrials.gov) - P2 | N=150 | Recruiting | Sponsor: Astellas Pharma Global Development, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open

Carbene reactive metabolite explains the hepatotoxicity of the hot flashes drug fezolinetant: A DFT investigation. (PubMed, Bioorg Chem) - "Reactions with model nucleophiles (MeOH, H2O, MeNH2, and MeSH) show that Fezo-carbene is likely to form thiol adducts. In summary, these results give vital insights into the metabolic mechanisms of fezolinetant's hepatotoxicity and are likely to be useful for the design of less-toxic analogues."

Journal • Hepatology • Liver Failure

Efficacy and safety of fezolinetant and elinzanetant for vasomotor symptoms in postmenopausal women: A systematic review and meta-analysis. (PubMed, Maturitas) - "Fezolinetant and elinzanetant are effective options for managing vasomotor symptoms. However, further research is needed to compare these treatments directly and evaluate their long-term safety profiles across different patient populations."

Journal • Retrospective data • Review

Fezolinetant and Elinzanetant Therapy for Menopausal Women Experiencing Vasomotor Symptoms: A Systematic Review and Meta-analysis. (PubMed, Obstet Gynecol) - "In this meta-analysis, consistent results suggest that fezolinetant and elinzanetant are associated with beneficial outcomes in menopausal women with vasomotor symptoms. Elinzanetant provided a larger effect size in vasomotor symptom frequency and severity reduction and greatly improved sleep quality compared with fezolinetant."

Clinical • Journal • Retrospective data • Review • Gynecology • Pain

Will elinzanetant, a neurokinin receptor antagonist, have a role in the treatment of hot flashes? (PubMed, Expert Opin Pharmacother) - "Fezolinetant does not have a clear-cut effect on sleep disturbances independent of VMS. Only, if elinzanetant can be shown to independently reduce sleep disturbances, it may have an advantage over fezolinetant."

Journal • Review • CNS Disorders • Sleep Disorder

A Study to Confirm if Fezolinetant Helps Reduce Hot Flashes in Chinese Women Going Through Menopause (clinicaltrials.gov) - P2 | N=150 | Not yet recruiting | Sponsor: Astellas Pharma Global Development, Inc.

New P2 trial

A Study to Confirm if Fezolinetant Helps Reduce Hot Flashes in Women With Breast Cancer Who Are Having Hormone Therapy (clinicaltrials.gov) - P3 | N=540 | Recruiting | Sponsor: Astellas Pharma Global Development, Inc. | Trial completion date: Aug 2027 ➔ Sep 2028

Trial completion date • Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor

Safety of Fezolinetant for Treatment of Moderate to Severe Vasomotor Symptoms Due to Menopause: Pooled Analysis of Three Randomized Phase 3 Studies. (PubMed, Adv Ther) - P3 | "Pooled data confirm the safety and tolerability of fezolinetant over 52 weeks."

Clinical • Journal • P3 data • Retrospective data • Back Pain • CNS Disorders • Hepatology • Infectious Disease • Insomnia • Liver Failure • Musculoskeletal Pain • Nephrology • Novel Coronavirus Disease • Oncology • Pain • Respiratory Diseases • Sleep Disorder • Solid Tumor

Fezolinetant's efficacy and safety in treatment of vasomotor symptoms in postmenopausal women: a meta-analysis and GRADE evaluation of randomized controlled trials. (PubMed, Eur J Med Res) - "Fezolinetant is efficient and well-tolerated in the treatment of postmenopausal women with VMS."

Clinical • Journal • Retrospective data

Kisspeptin and Neurokinin B: roles in reproductive health. (PubMed, Physiol Rev) - "Indeed, Fezolinetant, a neurokinin 3 receptor antagonist, has recently received Food and Drug Administration (FDA) approval for clinical use to treat menopausal vasomotor symptoms. Herein, we discuss the roles of kisspeptin and NKB in human physiology, including in the regulation of puberty, menstrual cyclicity, reproductive behavior, pregnancy, menopause, and bone homeostasis. We describe how perturbations of these key physiological processes can result in disease states and consider how kisspeptin and NKB could be exploited diagnostically, as well as therapeutically to treat reproductive disorders."

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Effect of fezolinetant on patient-reported quality-of-life outcomes: Data from a phase 3b study (DAYLIGHT) of the treatment of moderate to severe vasomotor symptoms associated with menopause in women considered unsuitable for hormone therapy. (PubMed, Maturitas) - "Patient-reported outcomes demonstrate that reductions in VMS frequency with fezolinetant treatment were associated with improvements in QOL."

Clinical • HEOR • Journal • P3 data • CNS Disorders • Depression • Mood Disorders • Psychiatry • Sleep Disorder

Safety update: EMA and FDA warn of liver problems with ▼fezolinetant. (PubMed, Drug Ther Bull) - No abstract available

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