Revolutionizing menopause management: A deep dive into fezolinetant

Contemporary OB/GYN:

Hi, I'm Celeste Krewson with Contemporary OB/GYN and I'm here with Dr. Pinkerton to discuss the FDA approval of fezolinetant for managing menopause symptoms in woman. Do you want to introduce yourself?

JoAnn Vensko Pinkerton, MD:

Yes, Hello, I'm Dr. JoAnn Pinkerton, Professor of Obstetrics and Gynecology at the University of Virginia and The Menopause Society credential menopause specialist.

Contemporary OB/GYN:

And to get started, can you provide some insights into the clinical efficacy and safety of fezolinetant, and how these findings compare with existing treatments for hot flashes?

JoAnn Vensko Pinkerton, MD:

So, fezolinetant works by blocking the neurokinin B binding to the KNDy neurons in the hypothalamus, reducing the neuronal activity and reducing hot flashes, and is highly effective. It's been tested in clinical trials of more than 2000 women, and in 2 of the phase 3 clinical trials, fezolinetant 45 milligrams reduced the frequency of the hot flashes by about 65%, significantly more than placebo and similar to the 75% reduction seen with hormone therapy. And this was at 12 weeks sustained them before the big extension trials. Importantly it was very rapid, the efficacy and rejection of hot flashes, frequency, and severity was evident within a week. And then we had some side effects and about 1% to 2% of clinical trials there were headaches, abdominal pain, diarrhea, insomnia, back pain, hot flushes, or some reversible elevated hepatic examinations. And there's a 52-week control safety trial also confirmed safety for the study.

Interesting fezolinetant doesn't contain estrogen. So, there's no adverse effects on the endometrium and there's no loss of bone density. And increases in the test you're isolated in return to baseline the GME treatment or afterwards. Now a couple of other issues that they've come up with this is that they do recommend monitoring level functions on baseline and then every 3 months for 9 months, and then you need to avoid these moderate CYP-118 inhibitors, which includes things like antidepressants.

Contemporary OB/GYN:

That's all really reassuring. So, in your opinion, what type of menopausal women would benefit most from fezolinetant? Are there any specific patient profiles or conditions that may make the treatment more favorable than others?

Pinkerton:

I’m going to make that into 2 questions. So, the women who don't have contraindications from therapies are likely going to remain the first choice for women who are close to menopause, under 60, within 10 years of menopause, because it not only leaves the hot flushes, but it gives additional benefits on bone loss, on treating vaginal dryness and dyspnea. But it does have side effects and risks, and there's this large, unmet need for an effective and safe therapy for women who can’t take risks. That’s where this new therapy comes in, because fezolinetant really works on hot flashes. So, it makes it a great non-hormone non-estrogen option for women who have moderate-to-severe hot flashes. And there was a segment of data presented at a 2023 meeting, which showed that it was affected among diverse populations, like Black, obese or non-obese, younger or older than 55, whether or not women smoked or have smoked.

So, that's really reassuring that they could take it, but there are some specific patients that I think about, and that's when they have estrogen sensitive cancers, breast cancer, endometrial cancer, occurs when women are at high risk of breast cancer. And then we have a group of women who might have had heart disease or stroke, deep vein thrombosis, those who have had severe endometriosis, where we don't want to stimulate the endometriosis with estrogen. And women who have migraine headaches, all more who have headaches that worsen on hormone therapy. Some for some very specific reason that we consider as well as women who just don't want to take them.

Contemporary OB/GYN:

So how can physicians go about recommending fezolinetant to their patients?

Pinkerton:

Well, I tell my patients that this new therapy works on the neurotransmitters in the brain, and it works to block the negative effects of lack of estrogen, and this is what leads to the fewer hot flashes and sweats and improve sleep. And then if a woman comes in and she's having 7 to 10 hot flashes a day with soaking sweats, I'm going to review all the options and discuss the effectiveness and the potential side effects of each. Then if women are interested in fezolinetant, I tell them it is almost as effective hormone therapy and give them something to read, how to sign up for savings plans, because it is costly, and discuss potential pathways to make it cost effective. I also discuss the liver function test at baseline every 3 months for 9 months, and a lack of data beyond 92 weeks. And then I have to check their medications to make sure that there's no contraindications. Let me share my first patient story. She had advanced breast cancer on an inhibitor. She tried many non-hormone options, she couldn't get any relief. She had frequent hot pushes during the day, but also soaking night swears, so she wasn't sleeping and she was miserable. After 2 weeks on fezolintetant, she said, “I have my life back, I can sleep again.” And 3 months after being on the medication, she's back working, she notes a dramatic improvement in quality of life. And she says, “I never want to go off.” The only issue I only have 52-week data.

Contemporary OB/GYN:

That's great. And in the broader context of menopause care, how do you see fezolinetant, fitting into a comprehensive treatment plan?

Pinkerton:

Severe vasomotor symptoms impact a woman's ability to function at all or work, it affects relationships, decreases quality of life, is associated with workplace absenteeism and increased healthcare costs. So, if we can reduce symptoms of menopause, this is going to allow women to function at a much higher level, and then we can identify other problems that goes along as women age.

Contemporary OB/GYN:

Thank you. We're just about ready to wrap up but it's anything you want to add first?

Pinkerton:

The downside of the medication is cost, trying to get it preauthorized and we need to use a special mail order pharmacy that need to check the liver function tests at baseline and every 3 months for 9 months, and the lack of data we don't get up to 2 weeks. But having said that, we've been able to jump through hoops and the patients have been extremely pleased with the results and grateful, and it's important to note also that there are some additional neurokinin receptor antagonists which are in development which may help even more. We need to wait for results to find out the safety and effectiveness. The great news is we have available, new, non-hormone, non-estrogen therapy for women.