On May 12, the U.S. Food and Drug Administration (FDA) approved VEOZAHTM (Fezolinetant), 45 mg once daily for the treatment of moderate to severe vasomotor symptoms (VMS) brought on by menopause, according to Astellas Pharma US, Inc. The first nonhormonal neurokinin 3 (NK3) receptor antagonist to be approved for the treatment of menopausal-related VMS is VEOZAH.
Before menopause, there is a balance between estrogens (hormones made by a woman’s ovaries) and neurokinin B (NKB), a brain chemical. This balance regulates the body’s temperature control center located in a specific area of the brain. As the body goes through menopause, estrogens decline and this balance is disrupted. This imbalance can lead to very uncomfortable symptoms called VMS. VEOZAH helps to restore the balance by blocking NKB in the temperature control center to reduce the number and intensity of hot flashes.
About VEOZAH
- Active ingredient: – Fezolinetant
- Description– VEOZAH (fezolinetant) is a neurokinin 3 (NK3) receptor antagonist indicated for the treatment of moderate to severe vasomotor symptoms (VMS) due to menopause. VEOZAH is not a hormone. VMS are the feelings of warmth in the face, neck, and chest, or sudden intense feelings of heat and sweating (“hot flashes” or “hot flushes”). VEOZAH works by blocking neurokinin B (NKB) +binding on the kisspeptin/neurokinin B/dynorphin (KNDy) neuron to modulate neuronal activity in the thermoregulatory center of the brain (the hypothalamus) to reduce the frequency and severity of moderate to severe VMS due to menopause.
- IUPAC-:-(4-fluorophenyl)-[(8R)-8-methyl-3-(3-methyl-1,2,4-thiadiazol-5-yl)-6,8-dihydro-5H-[1,2,4]triazolo[4,3-a]pyrazin-7-yl]methanone
- CAS RN:-1629229-37-3
- Originator :-Euroscreen
- Developer :-Astellas Pharma
- Indication:- Vasomotor symptoms (Hot Flash Treatment in Menopausal Women)
- Mechanism of Action-: Neurokinin 3 receptor antagonists
- FDA Approved: First approved May 12, 2023
- Patent disclosures – WO2014154895 (PCT/EP2014/056367), a novel compound patent filed by Euroscreen in the year 2014. This disclosure further provides methods of treatment and/or prevention of depression, anxiety, psychosis, schizophrenia, psychotic disorders, bipolar disorders, cognitive disorders, Parkinson’ s disease, Alzheimer’s disease etc. Additionally, WO2016046398 (PCT/EP2015/072167), a process patent talks about novel chiral synthesis of compound.
- Expiry based on international application – March 28, 2034
- Side effects of VEOZAH include:
- stomach (abdominal) pain
- diarrhea
- difficulty sleeping (insomnia)
- back pain
- hot flashes or hot flushes
- Dosage form: Tablets
About the BRIGHT SKY™ Phase 3 Program
The BRIGHT SKY pivotal trials, SKYLIGHT 1™ (NCT04003155) and SKYLIGHT 2™ (NCT04003142), enrolled over 1,000 women with moderate to severe VMS. The trials are double-blinded, placebo-controlled for the first 12 weeks followed by a 40-week treatment extension period. Women were enrolled at over 180 sites within the U.S., Canada and Europe. SKYLIGHT 4™ (NCT04003389) is a 52-week double-blinded, placebo-controlled study designed to investigate the long-term safety of Fezolinetant. For SKYLIGHT 4, over 1,800 women with VMS were enrolled at over 180 sites within the U.S., Canada and Europe.
Clinical Studies
Effects On Vasomotor Symptoms In Postmenopausal Women
The efficacy of VEOZAH for the treatment of moderate to severe vasomotor symptoms due to menopause was evaluated in the first 12-week, randomized, placebo-controlled, double-blind portion of each of two phase 3 clinical trials. In each of these two trials, after the first 12 weeks, women on placebo were then re-randomized to VEOZAH for a 40-week extension to evaluate safety for up to 52 weeks total exposure.
In Trials 1 (NCT04003155) and 2 (NCT04003142), 1022 women (522 in Trial 1 and 500 in Trial 2) who had a minimum average of 7 moderate to severe vasomotor symptoms per day were randomized to one of two doses of fezolinetant (including the 45 mg dosage strength) or placebo. Randomization was stratified by smoking status.
The mean age of the postmenopausal women was 54 years. Women self-identified as Caucasian (81%), African American (17%), Asian (1%), and Hispanic/Latina ethnicity (24%). The study population included menopausal women with one or more of the following: prior hysterectomy (32.1%), prior oophorectomy (21.6%), or prior hormone therapy use (19.9%). Those who were on prior hormone therapy underwent a wash-out period prior to trial participation.
The co-primary efficacy endpoints for both trials were the mean change from baseline in moderate to severe vasomotor symptoms frequency and severity to Weeks 4 and 12. Data from each trial demonstrated statistically significant and clinically meaningful (≥ 2 hot flashes over 24 hours) reduction from baseline in the frequency of moderate to severe vasomotor symptoms for VEOZAH 45 mg compared to placebo at Weeks 4 and 12. Data from each trial also demonstrated a statistically significant reduction from baseline in the severity of moderate to severe vasomotor symptoms (over 24 hours) at Weeks 4 and 12 for VEOZAH 45 mg compared to placebo.
About Astellas Pharma
Astellas Pharma Inc. is a pharmaceutical company conducting business in more than 70 countries around the world. We are promoting the Focus Area Approach that is designed to identify opportunities for the continuous creation of new drugs to address diseases with high unmet medical needs by focusing on Biology and Modality. Furthermore, we are also looking beyond our foundational Rx focus to create Rx+® healthcare solutions that combine our expertise and knowledge with cutting-edge technology in different fields of external partners. Through these efforts, Astellas stands on the forefront of healthcare change to turn innovative science into VALUE for patients.
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