Veozah (fezolinetant) / Astellas - LARVOL DELTA

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

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 event • Journal • Fatigue • Pain • Women's Health

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

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

New P2 trial • Cardiovascular

The Efficacy of Fezolinetant for the Treatment of Vasomotor Symptoms due to Menopause in Individuals with and without Diabetes Mellitus: A Pooled Phase 3 Analysis (ENDO 2025) - P3 | "Conclusions Fezolinetant can be regarded as an effective treatment for moderate to severe VMS in individuals with and without diabetes mellitus. Further investigations are warranted in this population."

Clinical • P3 data • Diabetes • Metabolic Disorders

Novel Pharmacotherapies for Menopausal Symptoms. (PubMed, Obstet Gynecol) - "Novel pharmacologic treatments for VMS have emerged in recent decades, some of which are already approved by the U.S. Food and Drug Administration (FDA) (eg, fezolinetant, a neurokinin 3B antagonist), and others are poised to seek FDA approval (eg, elinzanetant, a dual neurokinin 1B and 3B antagonist, and estetrol, a natural estradiol derivative that is unique to the pregnant state). Oxybutynin was shown to be effective for VMS and could provide additional benefits against overactive bladder, but long-term safety data are needed before wider utilization can be recommended."

Journal • CNS Disorders • Epilepsy • Overactive Bladder

Nonhormonal treatments for vasomotor symptoms. (PubMed, Curr Opin Obstet Gynecol) - "Women who cannot use or wish to avoid hormones have a number of nonhormonal options to choose from to treat hot flashes. New science elucidating the biology of hot flashes holds great promise for highly effective treatments that do not have off-target effects."

Journal

Hopes and cautions with neurokinin antagonists for the management of vasomotor symptoms. (PubMed, Maturitas) - No abstract available

Journal

Brain-Selective Estrogen Therapy to Prevent Menopausal Hot Flushes in a Primate Model (ENDO 2025) - "Recently, the FDA approved the neurokinin-3 antagonist fezolinetant for HF treatment, which modulates the activity of the neurokinin-B neurons involved in thermoregulation...Post OVX peripheral E2 levels were low/undetectable and DHED treatment did not result in any increase, indicating DHED treatment yields negligible circulating E2 despite being as effective as oral EE for HF. These findings underscore the effectiveness of DHED as a novel, innovative, and safe therapy of menopausal HFs without unwanted side effects in the periphery."

CNS Disorders • Depression • Mood Disorders • Nephrology • Oncology • Psychiatry • Renal Disease

Development of a Highly Potent Neurokinin‑3 Receptor Inhibitor: Design, Synthesis, and Evaluation. (PubMed, ACS Med Chem Lett) - "Despite this potential, only one NK3R ligand (ESN-364) has been clinically approved to date...Notably, 22i exhibited an enhanced membrane permeability and high oral bioavailability. In vivo efficacy studies revealed that oral 22i effectively suppressed luteinizing hormone levels, supporting its potential for further optimization."

Journal

Pharmacokinetics and Safety of Fezolinetant in Women with Hepatic or Renal Impairment. (PubMed, J Clin Pharmacol) - "In conclusion, hepatic impairment affects the metabolism of fezolinetant as shown by progressive increases in systemic exposure. Marginal impacts were noted in women with renal impairment."

Journal • PK/PD data • Hepatology • Renal Disease

Targeting vasomotor symptoms with the new drug fezolinetant - an expert overview. (PubMed, Gynecol Endocrinol) - "Fezolinetant is a precision drug as it targets the pathological mechanism of VMS showing some effect also on sleep disturbances. Given how variable the experience of menopause is, it is important to offer individualized treatment options to women who suffer from menopause-related symptoms and let them be part of the shared decision making."

Journal • Review • CNS Disorders • Sleep Disorder

Pharmacological Treatments for Menopausal Vasomotor Symptoms: A Systematic Review and Bayesian Network Meta-Analysis of Efficacy and Safety. (PubMed, Eur J Obstet Gynecol Reprod Biol) - "Conjugated estrogens and drospirenone with estradiol are the most effective options for reducing VMS frequency and severity, and Fezolinetant and Elinzanetant showed moderate efficacy, with overall similar safety across treatments."

Journal • Retrospective data • Review

Fezolinetant for vasomotor symptoms in postmenopausal women. (PubMed, Proc (Bayl Univ Med Cent)) - No abstract available

Journal

Efficacy and safety of fezolinetant for vasomotor symptoms in postmenopausal women: a comprehensive systematic review and meta-analysis of randomized controlled trials. (PubMed, Proc (Bayl Univ Med Cent)) - "Given fezolinetant's potential for liver enzyme elevations, it is essential to monitor liver function at baseline and regularly thereafter (monthly for the first 3 months and at 6 and 9 months) to ensure patient safety. Further studies with larger sample sizes are needed to confirm these findings."

Journal • Retrospective data

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

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

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=1003 | Active, not recruiting | Sponsor: Astellas Pharma Global Development, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Real-world evidence