Veozah (fezolinetant) / Astellas - LARVOL DELTA

Where do neurokinin receptor antagonists fit into management of menopausal vasomotor symptoms? (PubMed, JAAPA) - "To address this gap, nonhormonal therapies have been developed and investigated. Two newer options, fezolinetant and elinzanetant, directly target hypothalamic pathways involved in thermoregulation through modulation of neurokinin B. Clinical studies of these selective neurokinin B receptor antagonists demonstrate reduced frequency of vasomotor symptoms with their use, positioning them as promising options for individuals who are unable or unwilling to pursue hormone-based treatment."

Journal • Review

Liver Safety of the Dual Neurokinin-1/-3 Receptor Antagonist Elinzanetant. (PubMed, Drug Saf) - "The aggregated phase 1‒3 clinical data, supported by preclinical toxicology and individual case adjudications of participants with elevated liver enzymes, suggest that there is a low risk of liver toxicity for elinzanetant. On the basis of these data, liver test monitoring was considered unnecessary in clinical practice by the LSMB (video abstract available online). Supplementary file2 (MP4 73923 KB)."

Journal • Hepatology • Liver Failure

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

Trial completion

Comparative Efficacy of Elinzanetant Versus Other Non-Hormonal Pharmaceutical Therapies for the Treatment of Moderate-to-Severe Vasomotor Symptoms Associated With Menopause: A Network Meta-Analysis. (PubMed, BJOG) - "In this indirect comparison, elinzanetant showed superior or comparable efficacy to NKT or nHT in reducing the frequency and severity of VMS, along with improving sleep disturbances, supporting its role in VMS management."

Journal • Retrospective data • Review • CNS Disorders • Sleep Disorder

Fezolinetant for the Improvement of Vasomotor Symptoms in Breast Cancer Patients Taking Endocrine Therapy, VENT Trial (clinicaltrials.gov) - P2 | N=9 | Terminated | Sponsor: University of Michigan Rogel Cancer Center | N=36 ➔ 9 | Trial completion date: Oct 2026 ➔ Nov 2025 | Recruiting ➔ Terminated | Trial primary completion date: Jul 2026 ➔ Oct 2025; Lack of Patient Interest

Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Breast Cancer • Oncology • Solid Tumor

GRACE: A Study in Germany to Learn About the Value of Fezolinetant in Treating Hot Flashes and Night Sweats in Women During Menopause (clinicaltrials.gov) - P=N/A | N=105 | Active, not recruiting | Sponsor: Astellas Pharma Europe Ltd.

New trial

OPTION-VMS: First real-world fezolinetant effectiveness and safety data, including objective sleep data, in a phase 4 longitudinal, observational study of non-hormonal treatments for bothersome menopause-associated vasomotor symptoms (ISGE 2026) - "Interventions: Non-HT treatments: fezolinetant (an NK3R antagonist approved for moderate to severe VMS associated with menopause); SSRIs/SNRIs; and other non-HTs (e.g., gabapentin, oxybutynin). Fezolinetant treatment in OPTION-VMS was associated with statistically significant improvements in VMS bother, objective and subjective sleep indices, and menopause-related QoL. Preliminary analysis of OPTION-VMS supports the efficacy, safety, and tolerability of fezolinetant in the real-world setting, consistent with fezolinetant clinical trials and network meta-analyses, helping healthcare professionals make informed treatment decisions."

Clinical • Observational data • P4 data • Real-world • Real-world evidence

ISGE 2: Managing menopause: fezolinetant for the targeted treatment of vasomotor symptoms (ISGE 2026) - "Sponsored by Astellas"

Exploring fezolinetant: from clinical trials to clinical practice (ISGE 2026) - "Sponsored by Astellas"

Clinical

Trial in Progress: HIGHLIGHT 1 - A randomized, placebo-controlled, double-blind, phase 3 clinical study to investigate the efficacy and safety of fezolinetant for treatment of moderate to severe vasomotor symptoms (hot flashes) in women with stage 0 to 3 hormone receptor-positive breast cancer who are receiving adjuvant endocrine therapy (ISGE 2026) - P3 | "Adjuvant endocrine therapy, e.g., tamoxifen and aromatase inhibitors, can lead to premature menopause and vasomotor symptoms (VMS). To confirm if fezolinetant helps reduce treatment-induced VMS in women with stage 0-3 hormone receptor-positive breast cancer who are receiving hormone therapy."

Clinical • P3 data • Basal Cell Carcinoma • Breast Cancer • CNS Disorders • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Non-melanoma Skin Cancer • Oncology • Sleep Disorder • Solid Tumor • Women's Health

Effect of fezolinetant on weight, waist circumference, BMI, and BRI: data from phase 3, randomised, double-blind, placebo-controlled studies (SKYLIGHT 1, 2, and 4) over 52 weeks (ISGE 2026) - "There was no change in weight, waist circumference, or BMI with fezolinetant 30 mg and 45 mg over 52 weeks. BMI had no discernible effect on safety findings in participants treated with fezolinetant."

Clinical • P3 data

Focusing on the Menopausal Transition to Improve Mid-Life Women's Health (clinicaltrials.gov) - P2/3 | N=200 | Not yet recruiting | Sponsor: University of Colorado, Denver | Initiation date: Oct 2025 ➔ Mar 2026

Trial initiation date • Cardiovascular • Obesity • Women's Health • CXCL8

Fezolinetant for Treating Hot Flashes in Men With Prostate Cancer (clinicaltrials.gov) - P2 | N=32 | Recruiting | Sponsor: University of Vermont | Not yet recruiting ➔ Recruiting | Initiation date: Aug 2025 ➔ Dec 2025

Enrollment open • Trial initiation date • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Repurposing sulfonamide drugs as anticancer ligands and understanding its properties through density functional theory. (PubMed, Comput Biol Chem) - "The drugs Tolazamide, Fezolinetant, Ensulizole, Taurolidine, Acetohexamide, Isoxicam, Sulfamethizole, Sulfamethoxazole, Sulfapyridine, Sulfaphenazole, and Dodecyl sulphate were observed to exhibit high molecular volume, polarizability, dipole moment and significant HOMO, LUMO values, which are recommended for further quantum mechanical calculations...Quantum mechanical calculations will be performed on the optimal docking poses in future work. Keywords: Sulfonamide drugs, Docking, Histone deacetylases, Lipinsk's rule, Binding affinity."

Journal • Infectious Disease • Oncology

Piperazinotriazole-based NK3R antagonists: Rational design, synthesis, and identification of an orally active lead compound. (PubMed, Eur J Med Chem) - "The neurokinin-3 receptor (NK3R) has emerged as a promising non-hormonal therapeutic target for menopausal hot flashes, with fezolinetant being the only clinically approved NK3R antagonist to date. To overcome this therapeutic limitation, we designed a series of imidazolepiperazine derivatives (17a-17c, 21, 23a-23u), among which 23i(R) demonstrated superior pharmacological properties including potent NK3R inhibition (IC50 = 65.42 ± 6.54 nM), strong target binding (IC50 = 53.61 ± 3.67 nM), excellent membrane permeability (Papp A-B = 27.3 × 10-6 cm/s; ER = 0.53), and remarkable oral bioavailability (165 %). In ovariectomized rat models, 23i(R) effectively suppressed luteinizing hormone levels while exhibiting favorable pharmacokinetics and tolerability, establishing it as a promising clinical candidate for further development as a next-generation NK3R antagonist."

Journal

Expression of Concern: Fezolinetant and Elinzanetant Therapy for Menopausal Women Experiencing Vasomotor Symptoms: A Systematic Review and Meta-Analysis. (PubMed, Obstet Gynecol) - No abstract available

Journal • Retrospective data

Quantitative Systems Toxicology Modeling with DILIsym to Support Phase 3 Dose Selection for Fezolinetant. (PubMed, Clin Pharmacol Ther) - "These predictions aided discussions with internal and external stakeholders regarding dose selection and initiation of the phase 3 clinical studies. Phase 3 studies were subsequently completed and confirmed the efficacy and acceptable liver safety of fezolinetant at 30 and 45 mg QD, leading to drug approval at 45 mg QD."

Journal • P3 data • Hepatology • Liver Failure • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease

Tachykinin signaling defines distinct populations of glia in the enteric nervous system. (PubMed, Neuron) - "Genetic or pharmacological manipulation of NKB-TACR3 signaling disrupted the establishment of enteric glial populations during postnatal development and dynamically modulated intestinal motor behaviors in adult mice. Collectively, we delineate spatially, transcriptionally, and functionally distinct populations of enteric glia; identify one as an unanticipated target of TACR3 antagonists in clinical use; and establish this pathway as necessary for enteric glial diversification and function."

Journal

Utilization of fezolinetant for the treatment of moderate-to-severe vasomotor symptoms of menopause in a real-world setting. (PubMed, Menopause) - "Our findings highlight a need for future postmarketing safety and effectiveness studies, especially among survivors of breast cancer and women 65 years and older, who were excluded from the randomized controlled trials."

Journal • Real-world evidence • Breast Cancer • Oncology • Solid Tumor

Fezo-ADT: Proof-of-Concept Trial to Assess the Efficacy and Safety of Fezolinetant in Improving Vasomotor Symptoms in Men With Prostate Cancer Undergoing Androgen Deprivation Therapy (clinicaltrials.gov) - P2 | N=60 | Recruiting | Sponsor: Shehzad Basaria, M.D. | Not yet recruiting ➔ Recruiting

Enrollment open • Genito-urinary Cancer • Oncology • Prostate Adenocarcinoma • Prostate Cancer • Solid Tumor

A Study to Confirm if Fezolinetant Helps Reduce Hot Flashes in Japanese Women Going Through Menopause (clinicaltrials.gov) - P3 | N=410 | Completed | Sponsor: Astellas Pharma Inc | Active, not recruiting ➔ Completed

Trial completion

Innovative Drug Delivery Systems for Management of Menopausal Symptoms: A Systematic Review. (PubMed, Int J Womens Health) - "Non-hormonal Neurokini3 antagonists like fezolinetant, decreased VMS by 60% and benefited high-risk patients...DDSs offer personalized menopause management, balancing safety and efficacy. Future research should focus on pharmacogenomics, equity, and long-term safety of advanced DDSs, especially those using nanotechnology."

Journal • Review • Cardiovascular

Fezolinetant compared with elinzanetant for the treatment of vasomotor symptoms associated with menopause: A matching-adjusted indirect comparison. (PubMed, Maturitas) - "MAIC analysis found that fezolinetant and elinzanetant had a similar efficacy profile for reduction of VMS frequency and severity. Differences in reduction of sleep disturbances did not result in differences in QoL. Neurokinin receptor antagonists provide an alternative to HT and other non-HT options for the treatment of VMS associated with menopause."

Journal • CNS Disorders • Sleep Disorder

Hormone replacement therapy in gynecologic cancer: oncologic safety and alternative therapies. (PubMed, Int J Gynecol Cancer) - "Hormonal therapies for genitourinary syndrome of menopause, including vaginal estrogens, ospemifene, and vaginal dehydroepiandrosterone, have demonstrated efficacy in relieving symptoms and improving urogenital health...Non-hormonal therapies proven effective for managing vasomotor symptoms and sleep disturbances include cognitive behavioral therapy, clinical hypnosis, gabapentin, fezolinetant, and selective serotonin or serotonin-norepinephrine re-uptake inhibitors. Personalized treatment decisions should be guided by cancer type, recurrence risk, patient preferences, and quality-of-life considerations. It is essential to balance oncologic safety with symptom relief and long-term health outcomes in this growing population of cancer survivors."

Journal • Review • Cervical Cancer • CNS Disorders • Endometrial Cancer • Gynecologic Cancers • Oncology • Ovarian Cancer • Sarcoma • Sleep Disorder • Solid Tumor • Uterine Cancer • Vaginal Cancer • Women's Health

Elinzanetant (Lynkuet) for menopausal vasomotor symptoms. (PubMed, Med Lett Drugs Ther) - No abstract available

Journal