Astellas’ Non-Hormonal Drug for Hot Flashes Shows Promise in Two Phase 3 Trials

On February 19th, Astellas Pharma reported interim results of their non-hormonal treatment, Fezolinetant, against severe vasomotor symptoms (VMS). Treatment with either of two investigational doses provided a significant reduction in VMS, i.e., hot flashes and night sweats associated with menopause.  

After 12 months without a menstrual period, a woman is diagnosed with menopause. The average for a woman entering menopause in the US is 51 years old. It is a natural process, but for more than 50% of women, it is accompanied by severe or moderate vasomotor symptoms such as rapid heartbeat, sweat, a sudden feeling of warmth, anxiety, and others. These can take a toll on the quality of life of many women. The average duration for these symptoms is 4 years; however, around 10% of women will continue to suffer from VMS for up to 12 years.

Current therapies include hormone therapies like estrogen and estrogen plus progesterone. However, estrogen can increase the risk of developing endometrial cancer, and some women experience progesterone-related side effects. Although other non-hormonal therapies exist, more options are necessary to address the need.


Fezolinetant Evaluating SKYLIGHT Trials

Fezolinetant is a small molecule antagonist of the neurokinin-3 receptor (NK3R). It works by blocking the interaction of the receptor with its ligand in the area of the brain that controls body temperature. It was first developed by Ogeda, a company that Astellas later acquired in 2017.

The efficacy of Fezolinetant was determined in two double-blinded, placebo-controlled, multi-center, Phase 3 clinical trials. Over 1000 women were enrolled in the trials that consisted of a once-daily dose with 30 or 45 mg of Fezolinetant for 12 weeks and followed by a 40-week active treatment extension period. Women receiving Fezolinetant showed a significant decrease in the frequency and the severity of moderate to severe VMS at 4 and 12 weeks compared to the placebo group. Fezolinetant was well tolerated, with less than 2% of patients reporting adverse effects. The most common adverse effect was headaches.

“We are encouraged by these results for Fezolinetant, which mark the first Phase 3 data in a new category of selective neurokinin-3 (NK3)-targeted treatments for moderate to severe vasomotor symptoms,” said Salim Mujais, M.D., Senior Vice President and Therapeutic Area Head, Medical Specialties, Astellas. 

“Vasomotor symptoms can add a significant burden and impact the quality of life for women. We are hopeful that with Fezolinetant, we will be able to deliver a novel non-hormonal treatment option.”


Crowded Market

There is no approved medication for VMS treatment that targets the same mechanism as Fezolinetant, making it a first-in-class. However, several other non-hormonal therapies are available for the treatment of VMS. These include a low dose of antidepressants, as well as other medications such as Gabapentin, Pregabalin, Oxytutynin, Clonidine, to name a few. 

To carve a niche or take over this market, Fezolinetant would have to show superior efficacy and fewer side effects. Some of these questions may be answered at the end of the ongoing SKYLIGHT 4 trial to determine the long-term safety of this treatment.

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