https://intimmedicine.com/contact-us/

The Menopause Society meeting was the largest ever, reflecting growing interest in menopause treatments. The focus was on the psychosocial and psychological aspects of menopause, including mood changes and sleep disturbances. Dr. Simon presented results on a new non-hormonal treatment for menopausal hot flashes and other symptoms called Elinzanetant, which showed efficacy in reducing hot flash frequency and severity, improving sleep, and enhancing quality of life. There were also presentations on sleep disturbance, weight gain, and hair loss during menopause.

Hello everyone. My name is Dr. James Simon. I’m a reproductive endocrinologist, and clinical trial specialist in Washington DC, and clinical professor at George Washington University. I also have a private practice called IntimMedicine Specialists, also in Washington DC. It’s my pleasure to share a few thoughts with you today about this year’s Menopause Society meeting held in Chicago just last week. This year’s Menopause Society meeting was the largest in that organization’s history. I don’t know the final attendance, but the organization had to cut off in-person attendance because there were no more spaces. I guess that’s a good problem to have.

My belief is that there’s a great deal of interest about menopause hormone therapy and other therapies for this growing group of both patients and practitioners. And that interest is largely being driven by information on the internet through social media, rather than through traditional academic outlets. So let me just briefly tell you about my personal highlights from attending this meeting in Chicago. The meeting was organized, obviously by the organizing committee, but the head of the organizing committee, Dr. Soares, is a psychiatrist. And the meeting had a very strong emphasis on the psychosocial and psychological aspects of menopause to the benefit of the audience, because it’s often neglected. Mood changes as well as sleep disturbances were emphasized as part of this and was very important.

In addition, the program had a focus on the input of technology in the practice of medicine and in menopausal medicine specifically. For example, the potential and risks of artificial intelligence in the practice of menopausal and psychological medicine, as well as a focus on virtual reality and its potential in actual clinical practice. Fascinating subjects, all be them a little futuristic for my old bones. I had the opportunity to speak to the audience on the development of a new product not currently licensed anywhere in the world. A product being developed by Bayer Pharmaceuticals and called Elinzanetant, and it is an NK-III and NK-I receptor antagonist being developed for menopausal hot flashes and night sweats, and perhaps for sleep disturbance and anxiety or mood changes at menopause. And remember, this is a completely non-hormonal treatment in development.

I’d like to show you a few slides that I used in directing the audience to those new research findings. So here you can see the oral presentation that I made on behalf of all my colleagues, they’re listed here. I should point out that there are several past presidents of the Menopause Society and the International Menopause Society, as well as the ascending presidents of both those organizations. Likewise, I’d like to acknowledge my colleagues at Bayer who were part of this development. This presentation was the results of two phase three clinical trials, mostly efficacy focused, on this new chemical compound Elinzanetant for menopausal vasomotor symptoms and other associated symptoms of menopause.

Just briefly, this compound works to target two receptors in the central nervous system, which become hypertrophied and hyperactive with the fall of estradiol following menopause. These receptor systems are located in the hypothalamus where both ovulatory control occurs, but also where temperature regulation occurs, and we think other symptoms, including sleep and mood, are likewise represented in this part of the brain. So the design of the trial was very simple. Remember, these are two trials that were nearly identical in their design involving about 400 subjects placed both on Elinzanetant 120 milligrams daily for the better part of six months, and then a placebo group that was matched to them for the first 12 weeks of this study. And they were then switched to active treatment with Elinzanetant at the same dose. All the women in these studies had 50 or more moderate to severe hot flashes per week, a highly affected population chosen specifically for regulatory approval both in the EU and the US.

Here are some inclusions and exclusions, but they’re very common and focused on all developments for hot flash studies, at least in the US. In addition to the assessment of hot flashes, both frequency, the number of hot flashes per day, and severity, whether there were mild, moderate, or severe, there were two patient reported outcomes of importance in the care of postmenopausal women. They included the PROMIS SD F at 8b, total score. This is a standardized metric for sleep disturbance, and also the MENQAL total score, a validated short form menopause specific quality of life scale. So in this particular analysis, sleep and quality of life were also assessed in addition to the frequency and severity of hot flashes.

The participants in the study were enrolled, allocated, and analyzed as follows, probably less important for this group, but there were large numbers of individuals that enrolled at the beginning, but because they didn’t have adequate numbers or severity of hot flashes were not randomized in the final trial. Who were they? They were women about 55 years of age. About 80% of them were white, 20% Black or African-American, and about 7 to 10% self-identified as Hispanic. They were of relatively normal height and weight and a percentage of them, approximately 40%, had hysterectomy, and about 20% in addition to hysterectomy had oophorectomy.

Here are the results showing the first 12 weeks of the study. And here you have in blue or teal color, you have the Elinzanetant group and the pink represents placebo. And you can see that as early as week one, there was a statistically significant difference between the Elinzanetant group and placebo favoring Elinzanetant, a benefit that persisted through weeks four and week 12, the final endpoint of this first part of the efficacy study. Recalling that this was a randomized placebo-controlled trial for the first 12 wee.

For the second part of the trial for the remaining and the remaining trial, everyone in the trial received Elinzanetant as the placebo group was given the active treatment for this second phase of the study. They joined their colleagues who received Elinzanetant from the very beginning and had equal efficacy in terms of moderate to severe vasomotor symptoms. This slide is about frequency. The same exact findings occurred as it related to severity of hot flashes, as you can see here and here. With the medication ceasing to help in the post-treatment phase where everyone stopped using the active treatment.

As it related to sleep using the PROMIS SD SF 8b total score, you can see in similar to the hot flashes effect, a decrease in lost sleep. That is to say an improvement in the total score, which is downward on the trial. And then similarly, when the placebo-treated group switched over to Elinzanetant, an improvement in their sleep scores as well. As it related to the menopause specific quality of life score, you can see, again, improvement in the score in the quality of life score in the Elinzanetant group compared to placebo. And then the placebo when they were switched over to Elinzanetant joined their colleagues in an improvement in their menopause specific quality of life.

So in summary, I presented and was happy to show that Elinzanetant was effective for moderate to severe vasomotor symptoms, that it reduced those symptoms as early as the first week of active treatment compared to placebo. And the reductions in both frequency and severity of hot flashes persisted through the entire approximate six months of the study. And then both sleep and quality of life were improved in this design and study. And then just as a final conclusion, the safety of this, what I’ve just presented to you was largely an efficacy approach to evaluation of Elinzanetant. But I also presented a large safety study, the OASIS 3 study, at this same meeting, but in a different style and different presentation. I’ll show you that in just a moment.

Here is a poster presentation of the safety study that I mentioned in my previous efficacy presentation. This was presented as a poster, showing a one-year trial of Elinzanetant in real-world patients with some, but not nearly as severe, motor symptoms due to menopause. It involved approximately 300 subjects in both Elinzanetant and placebo, was randomized, and prospective, and demonstrated as you might expect from the previous sets of slides, efficacy of Elinzanetant as opposed to placebo for the entirety of the approximately one-year trial, demonstrating both a reduction in frequency and severity of hot flashes that were statistically significant. In addition, as I just presented, in the other studies, there was an improvement in both the menopause specific quality of life scale as well as sleep.

But in this study, long-term study, there was a big focus on safety. Safety, both in terms of adverse events experienced by the study subjects, but also the concern of this entire class of neurokinin modulators, a concern about liver safety. As other investigations in this class have shown some concerns about liver safety. And I’d like to point out this scattergram Figure 3 down here, as an example of how this product Elinzanetant demonstrated liver safety. This is a scattergram of the effects of Elinzanetant or placebo over the course of this one year study on liver function tests. And to cut to the chase, there were no significant patients with elevated liver function tests, satisfying the criteria of what’s called HY’s law. That’s H-Y apostrophe S, HY’s law where we worry about liver damage.

There are about 12 subjects in the whole study of more than 600 who had minor elevations of their liver function tests, that is to say ALT, for example. But they were exactly and equally distributed between those subjects that received placebo and those subjects that received active treatment. And they’re located in this little quadrant of this scattergram, recognizing that the solid circles and the open squares are about five subjects of each. So equally distributed between placebo and active treatment.

And our conclusions from this were that both Elinzanetant was capable of reducing moderate to severe hot flashes, but also improving sleep and menopause specific quality of life, with a favorable safety profile over the course of this 52 weeks of treatment. The side effect profile was, as had been presented previously with a small percentage less than 10% of subjects experiencing headache. Covid was covered as a potential adverse event, but was actually more prevalent in the placebo group than the active treatment group. But the major side effects headache, fatigue, and somnolence were in higher prevalence in the Elinzanetant group than the placebo group.

And that was our presentation of the safety of this new development for moderate to severe vasomotor symptoms. There were many other excellent presentations at this year’s Menopause Society meeting in Chicago. My favorites included an excellent presentation about sleep and sleep disturbance during menopause, about weight gain across the menopause transition and following menopause, and a wonderful presentation about hair loss in older menopausal and aging women with the importance of all of those endpoints in how we care for our menopausal patients. Thanks a lot for having me on today. I look forward to our next visit together.

For more information about menopausal health, contact Dr. Simon at IntimMedicine Specialists. To schedule an appointment, call our office at (202) 293-1000 or https://intimmedicine.com/contact-us/.