How fezolinetant changes management of hot flashes

Nanette F. Santoro, MD:

Sure. So let me just introduce myself. I'm Nanette Santoro. I'm Professor and Chair of ob-gyn at the University of Colorado School of Medicine, and I have been involved in studies of the new first in class, neurokinin 3 receptor antagonist called fezolinetant. And it's a specific antagonist of this specific receptor, which is really a breakthrough in the non-hormone treatment for hot flashes. It was just approved by the FDA in May. There are a number of compounds that are similar to this that have targeted this specific receptor, and they will be coming out probably in coming years, but we now have data on fezolinetant to talk about. It seems to be effective in reducing hot flashes, not quite of the magnitude as estrogen but awfully close. And it's been studied in the major pivotal trials, probably about 1000 to 1200 women worldwide that have been on placebo or active drug. So, we have data on thousands of women, and some of the secondary analyses at this meeting, one that I am involved in is looking at women who were considered unsuitable for hormone therapy because they have a contraindication. This could be a venous thromboembolism, heart disease, a reason that hormone therapy should not be given, women who are averse to hormone therapy, and women for whom it's a caution. So, there would be a concern that the hormone therapy might not be the best treatment for them. And regardless of those categories, the bottom line of what we saw was that all of those groups of women, when they took fezolinetant had similar magnitude of relief of hot flashes, both in terms of number and in terms of severity. So, your history doesn't matter so much. We have previously seen that women with different factors, smoking BMI, and things like that also get similar relief. So, this looks like it's something that should be broadly applicable to a number of different patient groups. And that's also encouraging because it sort of simplifies prescribing, because it is quite a mouthful to say an NK 3 receptor antagonist to your patient. But this is something that's on the neurons that govern the thermoregulatory center in the brain, and blocking them seems to bypass estrogen and seems to effectively block hot flashes.

Nanette F. Santoro, MD:

The pooled safety data is also presented here as a poster and it looks very good. When you look at overall treatment emergent adverse effects or ones that lead to drug discontinuation, they seem equivalent in both placebo and in fezolinetant groups. However, the FDA out of what I would call an abundance of caution has required women using this medication to have baseline and 3-, 6-, and 9-month liver function tests. I've personally just plug this into my medical record with a dot phrase that the patient understands they need to get that at baseline and then we check them. There are also a contraindication because of concern again about liver toxicity with compounds that are called SIP-182 inhibitors. And if you're confused by that, so am I. There's no real rhyme or reason as to what class of drugs they fall into. So, this includes medications like Pepcid commonly used, and things like Valacyclovir. But you kind of have to look at a patient's medication list to make sure that you've got all those interactions covered because she might be on something that's contraindicated for use with fezolinetant.

Nanette F. Santoro, MD:

I have been very pleased. I didn't expect it to work this well. I thought it would be maybe it's going to be just as good as the SSRIs are, but it seems to be better. In my patients I have encountered few side effects. The listed side effect most common is headache, and headache is the most common side effect you see with almost any drug in any study. So, there's some GI, some nausea, but I would say ¾ of the patients I am prescribing it for are happy with it and they want to continue it and it's giving them significant relief without any of the discussion, side effects, or off target effects that you get with the alternatives we have, only one of which is FDA approved.