Astellas’ non-hormonal VMS therapy gets FDA approval

U.S. Food and Drug Administration (FDA) has approved Veozah (fezolinetant), the first neurokinin 3 (NK3) receptor antagonist, to treat moderate to severe vasomotor symptoms (VMS) that arise from menopausal transition affecting up to 80% of women in East Asia and US between the ages of 40 to 65 years. (1)

The consent by FDA was granted to Astellas Pharma US, Inc, an affiliate of Tokyo-based Astellas Pharma Inc, that came into being in 2005 after merger of Yamanouchi Pharmaceutical Co., Ltd and Fujisawa Pharmaceutical Co., Ltd.

VMS presents through various symptoms such as hot flushes, which presents with a sudden feeling of heat in the face, neck and chest, often accompanied by flushing of the skin, perspiration, palpitations, and acute feelings of physical discomfort as well as night sweats. (2)

Grant of the approval was announced on 12 May 2023 with FDA saying, Veozah had, during clinical trials, demonstrated effectiveness to treat VMS.

Fezolinetant is the active ingredient in Veozah while the inactive ingredients in the tablet include ferric oxide, hydroxypropyl cellulose, hypromellose, low-substituted hydroxypropyl cellulose, magnesium stearate, mannitol, microcrystalline cellulose, polyethylene glycol, talc, and titanium dioxide. (3)

Patients would need to take one tablet that contains 45 milligram of fezolinetant orally, once a day, with or without food.

According to Astellas, Fezolinetant works by “blocking neurokinin B (NKB) binding on the kisspeptin/neurokinin/dynorphin (KNDy) neuron to moderate neuronal activity in the thermoregulatory center of the brain (the hypothalamus) to reduce the frequency and severity of moderate to severe VMS associated with menopause.”

Possible side effects of Veozah include possible liver injury that would present with symptoms such as nausea, vomiting, or yellowing of the skin and eyes.

Those restrained from taking Veozah include patients using with CYP1A2 inhibitors, those with known cirrhosis, severe renal damage or end-stage renal disease.

Astellas Pharma lists other most common side effects of Veozah such as abdominal pain, diarrhoea, insomnia, back pain, hot flush and elevated hepatic transaminases.

However, the European Medicines Agency (EMA), the Therapeutic Goods Administration (TGA), and Swissmedic, which are the medicine and drug regulatory agencies for the EU, Australia and Switzerland, are still reviewing Veozah before determining whether or not to approve for use.

Previously, some drug makers, such as TherapeuticsMD, had unveiled hormonal therapies to deal with VMS with FDA saying such therapies “may help relieve hot flashes, night sweats, vaginal dryness, or dyspareunia.” (4)

TherapeauticsMD’s BIJUVA (estradiol and progesterone) capsules 1 mg/100 mg, was granted approval by FDA in 2018 for the treatment of VMS.

At the time, TherapeuticsMD said the hormonal therapy was “the first and only FDA-approved bio-identical hormone therapy combination of estradiol and progesterone in a single, oral capsule for the treatment of moderate to severe VMS.” The bio-identical hormone therapy refers to estradiol and progesterone that are “molecularly identical to the hormones produced naturally in the woman’s body.” (5)

According to the North American Menopause Society, hormone therapy remains “the most effective treatment for VMS and the genitourinary syndrome of menopause and has been shown to prevent bone loss and fracture.” (6)

More VMS treatment options are expected when the third phase of clinical trials for Bayer’s elinzanetant, a non-hormonal treatment for VMS is complete.

Bayer said in 2021 clinical trials are meant to evaluate the efficacy and safety of elinzanetant for VMS during menopause as once-daily, oral, dual neurokinin-1,3 receptor antagonist.

Although there is no precise data on the rate of growth menopausal and post-menopausal symptoms globally, the number of women seeking treatment from vasomotor symptoms is likely to increase and so is the market for hormonal and non-hormonal therapies.

Bayer estimates more than one-third of women report severe symptoms, “which can last 10 years or more after the last menstrual period.” (7)

REFERENCES

1. https://www.fda.gov/news-events/press-announcements/fda-approves-novel-drug-treat-moderate-severe-hot-flashes-caused-menopause

2. https://www.who.int/news-room/fact-sheets/detail/menopause

3. https://www.astellas.com/us/system/files/veozah_usppi_2.pdf

4. https://www.fda.gov/media/130242/download

5. https://ir.therapeuticsmd.com/news-releases/news-release-details/therapeuticsmd-announces-fda-approval-tx-001hr-bijuvatm

6. https://www.menopause.org/docs/default-source/professional/nams-2022-hormone-therapy-position-statement.pdf

7. https://www.bayer.com/en/ca/bayer-starts-phase-iii-clinical-development-program-oasis-with-elinzanetant.