Veozah (fezolinetant) / Astellas - LARVOL DELTA

Precision pharmacology in menopause: advances, challenges, and future innovations for personalized management. (PubMed, Front Reprod Health) - "Non-hormonal options like SSRIs/SNRIs (40%-60% efficacy) and NK3R antagonists (fezolinetant, 50%-65% VMS reduction) suit contraindicated patients...Advancements underscore precision pharmacology's shift to individualized, non-hormonal treatments. Future priorities: biomarker-guided personalization, AI-driven discovery, and novel delivery systems to enhance efficacy, reduce risks, and improve QoL for menopausal women."

Journal • Review • Breast Cancer • Cardiovascular • CNS Disorders • Hormone Receptor Breast Cancer • Oncology • Osteoporosis • Rheumatology • Solid Tumor • Women's Health

FLASH-CV:: Finding Links Between Hot flASHes and CardioVascular Disease (clinicaltrials.gov) - P2 | N=80 | Not yet recruiting | Sponsor: Massachusetts General Hospital | Initiation date: Oct 2025 ➔ Jan 2026

Trial initiation date • Cardiovascular

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 | Not yet recruiting | Sponsor: Shehzad Basaria, M.D. | Initiation date: Aug 2025 ➔ Dec 2025

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

Early onset, maintenance of effect, and day-/night-time findings following fezolinetant treatment for moderate to severe vasomotor symptoms associated with menopause: A pooled phase 3 analysis. (PubMed, Maturitas) - P3 | "The onset of action for fezolinetant was observed from day 1 for VMS frequency and severity and was maintained for 52 weeks. Fezolinetant can provide rapid and prolonged relief from VMS."

Journal • P3 data

Data Mining and Bioinformatics Analysis of a Novel Adverse Event Signal of Fezolinetant: A Real-World Analysis of the US FDA Adverse Event Reporting System Database (ISPOR-EU 2025) - "The strong gene-binding affinities of fezolinetant suggest a potential link to dysarthria, warranting further pharmacoepidemiologic validation. These insights may support post-marketing surveillance and help clinicians monitor for dysarthria among patients administered with fezolinetant.Key Words: Fezolinetant, Dysarthria, Signal-Detection, Adverse Drug Reactions, Molecular docking"

Adverse events • Clinical • Real-world • Real-world evidence • GRM1

Fezolinetant Veoza™ As a Nonhormonal Treatment for Moderate to Severe Vasomotor Symptoms in Postmenopausal Women: A Systematic Literature Review and Meta-Analysis (ISPOR-EU 2025) - "Fezolinetant provides dose-dependent reductions in VMS frequency and severity. The 45mg dose exceeded the commonly accepted clinical benefit threshold of ≥2 VMS/day reduction, indicating a clinically meaningful benefit. These findings support fezolinetant 45mg as an effective and well-tolerated targeted non-hormonal treatment option for postmenopausal women, including those unsuitable for MHT."

Retrospective data • Review

FDA approves Veozah (Fezolinetant) for menopausal symptoms: a new nonhormonal option. (PubMed, Ann Med Surg (Lond)) - "Its targeted mechanism addresses the underlying neurochemical dysregulation associated with VMS, providing rapid and sustained symptom relief. As research continues to explore its long-term impact, fezolinetant represents a promising advancement in women's health, improving the management of menopausal symptoms and enhancing overall well-being."

FDA approval • Journal • Fatigue • Pain • Women's Health

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

Enrollment open • Breast Cancer • Oncology • Solid Tumor

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: Sep 2028 ➔ Jun 2027 | Trial primary completion date: Nov 2026 ➔ Aug 2026

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

Concentration-QTc Modeling to Support Clinical Development of Fezolinetant. (PubMed, Clin Pharmacol Drug Dev) - "The fezolinetant C-QTc relationship indicated no clinically relevant QT prolongation at therapeutic or supra-therapeutic doses of fezolinetant. Based on these modeling results as well as data from other clinical and non-clinical studies, no thorough QT/QTc (TQT) study was required for fezolinetant."

Journal • Cerebral Hemorrhage

A Study to Confirm if Fezolinetant Helps Reduce Hot Flashes in Japanese Women Going Through Menopause (clinicaltrials.gov) - P3 | N=410 | Active, not recruiting | Sponsor: Astellas Pharma Inc | Trial completion date: Mar 2026 ➔ Dec 2025 | Trial primary completion date: Feb 2026 ➔ Oct 2025

Trial completion date • Trial primary completion date

Neurokinin Antagonists to Treat Vasomotor Symptoms-Possible Implications for Long-Term Health and Disease. (PubMed, J Clin Med) - "Recent evidence indicates that fezolinetant, a neurokinin-3 receptor antagonist and elinzanetant, a neurokinin-1-3 receptor antagonist, diminish the frequency and severity of vasomotor symptoms. The causal relation of symptoms with cortisol levels and oxidative stress, and the reduction in cortisol and blood pressure by symptom improvements, support the possibility that neurokinin antagonists may decrease those factors linking menopausal symptoms with cardiovascular disease and osteoporosis. Dedicated studies are needed to test the hypothetical possibility that neurokinin receptor antagonists contribute to reduce the long-term burden of cardiovascular disease and osteoporosis of symptomatic women in post-menopause unwilling or with contraindication to the use of menopause hormone therapy."

Journal • Cardiovascular • CNS Disorders • Depression • Hypotension • Metabolic Disorders • Musculoskeletal Diseases • Orthopedics • Osteoporosis • Psychiatry • Rheumatology • Sleep Disorder

Practical considerations and emerging approaches for the management of vasomotor and sexual symptoms in breast cancer patients on endocrine therapies. (PubMed, Expert Rev Clin Pharmacol) - "Pharmacologic therapy for VMS has been centered on selective serotonin reuptake inhibitors and serotonin norepinephrine reuptake inhibitors, gabapentin, and clonidine...This review summarizes the current pharmacologic therapy for VMS, focusing on the practical considerations for use of the novel VMS (fezolinetant, elinzanetant) and libido agents (flibanserin, bremelanotide)...These novel agents are eagerly awaited therapeutic options; however, clinical trials excluded breast cancer patients. This review provides clinicians with relevant considerations to assess when recommending these therapies for patients with breast cancer, while awaiting ongoing research to give additional insights for best tailoring therapy for this patient population."

Journal • Review • Breast Cancer • Oncology • Solid Tumor

Advances in Pharmacotherapy for Menopausal Vasomotor Symptoms. (PubMed, Drugs) - "Fezolinetant (NK3 receptor antagonist) and the newly approved elinzanetant (NK1 and NK3 receptor antagonist) are non-hormonal treatment options approved for the treatment of VMS associated with menopause. A number of investigational agents are currently in phase 2 trials for potential future use for VMS; these include Q-122, PhytoSERM, NOE-115, GS1-144, and HS-10384. In this review, we highlight the recent advancements in our understanding of the pathophysiology of VMS and consider the current, new, and investigational treatment options for the treatment of VMS."

Journal • Review • Alzheimer's Disease • Cardiovascular • CNS Disorders • Cognitive Disorders • Coronary Artery Disease • Heart Failure • Sleep Disorder

OPTION-VMS: A Study Following Women in Menopause Treated With a Non-hormonal Therapy for Hot Flashes and Night Sweats (clinicaltrials.gov) - P=N/A | N=998 | Active, not recruiting | Sponsor: Astellas Pharma Global Development, Inc. | Trial completion date: Nov 2026 ➔ May 2026 | Trial primary completion date: Feb 2026 ➔ Aug 2025

Real-world evidence • Trial completion date • Trial primary completion date

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

Enrollment closed

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 | Initiation date: Jun 2025 ➔ Oct 2025

Trial initiation date • Breast Cancer • Oncology • Solid Tumor

Fezolinetant Can Reduce Menopause Symptoms in Women Who Cannot or Will Not Take Hormone Therapy. (PubMed, Am Fam Physician) - No abstract available

Journal

Genetics of Idiopathic Hypogonadotropic Hypogonadism. (PubMed, J Clin Res Pediatr Endocrinol) - "Despite these complexities, genetic studies of IHH have provided critical insights into fundamental neuroendocrine processes, most notably the recent elucidation of the KNDy (Kisspeptin, Neurokinin B, Dynorphin) neurons as the GnRH pulse generator. These discoveries have also informed the development of targeted therapies, exemplified by the recent FDA approval of fezolinetant, a neurokinin B receptor antagonist, for the treatment of menopausal vasomotor symptoms."

Journal • Endocrine Disorders • Infertility • Sexual Disorders

Pharmacokinetics, Tolerability, and Biomarker Profile of the Neurokinin 3 Receptor Antagonist Fezolinetant in Healthy Japanese Individuals: A 2-Part, Randomized, Phase 1 Study. (PubMed, Clin Pharmacol Drug Dev) - "This analysis shows that fezolinetant doses up to 180 mg had an acceptable safety, pharmacokinetic, and biomarker profile. This study clarifies the safety, pharmacokinetic, and biomarker profiles of fezolinetant in Japanese individuals."

Biomarker • Journal • P1 data • PK/PD data

Treatment of Menopausal Symptoms When Hormone Therapy Is Contraindicated. (PubMed, Semin Reprod Med) - "This review explores alternative nonhormonal treatments, including pharmacological options like selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, gabapentin, clonidine, and neurokinin receptor antagonists (e.g., fezolinetant), alongside nonpharmacological approaches such as lifestyle modifications, cognitive-behavioral therapy, and acupuncture. GSM management includes therapies such as vaginal estrogens, prasterone, and ospemifene, with tailored approaches necessary for cancer survivors. Emphasis is placed on individualized care, better patient education, and continued research into the safety and efficacy of these therapies to improve the QoL for postmenopausal women."

Journal • Cardiovascular • Oncology • Women's Health

Successes and failures of DILIsym (ACS-Fall 2025) - "DILIsym modeling has been instrumental in the guiding successful development of drugs where hepatotoxic potential was identified (e.g. fezolinetant), or where first in class candidates were abandoned due to liver toxicity observed in clinical trials (e.g. the CGRP small molecule drugs)...However, about 20% of drugs and dosing regimens demonstrated to be capable of causing liver toxicity in some patients (e.g. ketoconazole) give false negative results with the current DILIsym model. These false negative results seem likely to in part reflect relevant toxic metabolites not produced in the liver cell lines assayed, although attempts to use more metabolically competent liver culture models has not yet converted false negative results. It is also likely that there are relevant AOPs not currently assayed or represented in DILIsym (e.g. ER stress)."

Hepatology • Metabolic Disorders

Advent of NK3R Antagonists for the Treatment of Menopausal Hot Flushes: A Narrative Review. (PubMed, BJOG) - "Fezolinetant has received approval from drug regulatory authorities worldwide, with data from multiple clinical trials showing a marked 60%-80% reduction in the frequency and severity of daily moderate-severe VMS, including in those considered unsuitable for MHT. Very recently, elinzanetant has been approved by the MHRA in the UK for the treatment of VMS in menopause, though it has not yet been approved by the FDA in the US...Data from clinical trials identifying NK3R antagonists as novel therapeutic agents for menopausal VMS are reviewed. Finally, the current status of NK3R antagonists and future directions of study in this area are discussed."

Journal • Review

PERCEIVE: A retrospective, qualitative interview-based study of the impact of vasomotor symptoms associated with menopause on the lives of individuals who are not suitable candidates for hormone therapy. (PubMed, Maturitas) - P3 | "Vasomotor symptoms associated with menopause negatively impacted daily life, particularly sleep, among participants unsuited to hormone therapy. Many sought nonhormonal treatments but found them ineffective, costly, and unsatisfactory."

Interview • Journal • Retrospective data

The role of Fezolinetant in fear memory consolidation. (PubMed, Brain Res) - "Considering that Fezolinetant is currently a treatment for hot flashes in menopausal women, our results could be rapidly translated into clinical trials focused on treating or preventing fear-based disorders. Thus, these findings support the role of Tac2/NkB/Nk3R in fear memory consolidation and emphasize the importance of considering sex differences in the neurobiology of memory-related processes."

Journal • CNS Disorders • Mental Retardation • Mood Disorders • Post-traumatic Stress Disorder • Psychiatry