Treatment for menopause is entering a new age. New data by Bayer Pharmaceuticals – which has its U.S. headquarters in Whippany – showed that its experimental non-hormonal drug reduced the frequency and severity of menopause side effects, such as hot flashes and sleep disturbances. If the U.S. Food and Drug Administration approves Bayer‘s therapy, it would become the second non-hormonal drug for vasomotor symptoms.

In releasing the findings earlier this month from two late-stage clinical studies for elinzanetant, the German multinational said the results reinforce the oral, once-daily drug’s potential as a treatment option for women experiencing menopause. Bayer now plans to submit the results to the FDA this year.

During a March presentation to investors, Bayer’s pharmaceutical division head Stefan Oelrich described elinzanetant as a “potential blockbuster,” claiming the drug will be “capable of transforming the way menopausal symptoms are treated.”

An inevitable process of aging that happens between ages 45 and 55, menopause occurs when a woman’s hormone production declines and sets off a range of well-known symptoms that last an average of seven years.

By 2030, there will be 1.2 billion menopausal and postmenopausal women globally, with 47 million new entrants each year, according to the Mayo Clinic.

Abhishek Sharma, an associate professor in the Chemistry and Chemical Biology Department at Stevens Institute of Technology, noted that “while a very large number of women face menopause symptoms,” the drug pipeline “is very small.”

“Hormone replacement therapy has been the mainstay for treatment of menopause symptoms,” he said. “However, many patients have concerns regarding a greater risk of cancer.”

The more than 30 prescriptions on the market come in forms including estrogen-only or estrogen and progestin combination pills, patches, gels, creams and sprays. Despite the general safety of hormone treatments, the FDA cautions patients to take the lowest dose for the shortest amount of time due to their various health risks.

For some women, hormone medications may raise their chances of blood clots, heart attacks, strokes, gall bladder disease, endometrial cancer and breast cancer, according to the FDA.

More than just a flash

Elinzanetant works by targeting two receptors in the brain – NK-3, which regulates body temperature, and NK-1, which affects mood and sleep.

According to Bayer, elinzanetant met all research goals in two studies that included about 800 post-menopausal women. The newly reported results expand on positive top-line data Bayer published earlier this year and confirmed that the therapy outperformed a placebo over a 12-week window.

For the first and second study, Bayer respectively enrolled 396 and 400 women between the ages of 40 and 65 years with moderate to severe vasomotor symptoms. Participants either received a once-daily dose of elinzanetant or placebo and were evaluated over 26 weeks.

In the first study, Bayer reported treatment led to an average reduction of 3.29 occurrences of vasomotor symptoms at week four, and of 3.22 at week 12, as recorded by a hot flash daily diary. Significant decreases in symptom severity were also reported at weeks four and 12, compared to placebo.

In the second study, the drug reduced the frequency of symptom occurrence by an average of 3.04 at week four and by 3.24 at week 12. Participants in this study also reported significant lessening of severity, compared to those on placebo.

By 2030, there will be 1.2 billion menopausal and postmenopausal women globally, with 47 million new entrants each year. – Mayo Clinic

A similar medicine by Astellas Pharma was authorized last year by the FDA for hot flashes. Known as Veozah, the treatment also targets NK-3 and led to reductions in the frequency of vasomotor symptoms by an average of 2.5 and 2.6 at week 12, according to the results of clinical studies.

Daniel Abazia, a clinical associate professor at Ernest Mario School of Pharmacy at Rutgers University and director of RWJBarnabas Health’s medication-use safety and information center, said, “These results from elinzanetant’s … Phase III clinical trials are exciting news for women who suffer from moderate to severe hot flashes and potentially will provide a new tool in managing these symptoms.”

“Elinzanetant, is a dual neurokinin-1,3 (NK-1,3) receptor antagonist whereas fezolinetant [Veozah] is a neurokinin-3 (NK-3) receptor antagonist. Neurokinin is a specific neurotransmitter (cell signaler) in the hypothalamus of the brain that is linked to vasomotor symptoms during menopause. Neurokinin-1 is thought to be linked to the body’s internal thermostat,” Abazia explained.

Sharma pointed out, “Veozah’s label includes warnings about high liver blood test values and side effects such as back pain, stomach pain, insomnia and diarrhea. The new drug [elinzanetant] from Bayer is also non-hormonal but it has a slightly different mechanism than Veozah. It acts on two enzymes: neurokinin-1 (NK-1) and 3. Phase 3 clinical results of elinzanetant suggest that this new drug might have fewer side effect than Veozah.”

Both drugs are expected to pull in billions of dollars over the next decade, with Astellas’ therapy having a first-to-market advantage. In 2030, Veozah and elinzanetant are forecast to earn $1.8 billion and $1 billion in sales, respectively, a GlobalData analysis found.

Abazia noted there are a few other menopause-focused drugs in the works – including two early-stage candidates from Dare Bio. The first treatment is a hormone-based therapy for hot flashes and the second is a non-hormonal tamoxifen-based treatment for vulvar and vaginal atrophy.

Mitsubishi Tanabe Pharma also has a phase II drug, elismetrep, a TRMP8 antagonist targeted for peripheral neuropathic pain, for hot flashes, he pointed out.

The gender health gap

As a company that has long maintained a presence in women’s health research, Bayer’s portfolio includes Yasmin brand birth control pills and the Mirena intrauterine device.

In acquiring U.K.-based biotech KaNDY Therapeutics for $425 million in August 2020, Bayer obtained the rights to elinzanetant. At the time, Bayer said adding a novel non-hormonal treatment would help broaden its women’s health care pipeline.

However, within the past year, Bayer’s overall sluggish performance has triggered an overhaul under its new chief executive officer, Bill Anderson. As a result, the company is no longer prioritizing R&D investments in women’s health and is focused on four core therapeutic areas: oncology, cardiology, neurology and rare diseases/immunology.

In a statement to Fierce Biotech, a company spokesperson said Bayer sought to refine its “early innovation framework to concentrate on areas where we anticipate the best opportunities for delivering differentiated, high-value breakthrough medicines to patients.”

For a range of reasons – from perceived cost and risk to that fact clinical trials don’t work well for women who are pregnant or lactating – research into women’s health and development of new drugs and devices remains an underfunded area across the pharmaceutical industry.

Compared to conditions that mainly affect men, fewer resources are allocated toward researching those that mainly affect women. There are also weaker financial incentives to develop drugs for women’s health, according to a Citi Global Insights report on the gender health gap.

Citi Global went on to note that health care is still predominantly led by men and that only about a quarter of leadership positions at pharmaceutical companies are held by women. The executive makeup is something that shapes what innovations the sector focuses on, how seriously women are taken by health care providers and the treatments that reimbursement systems will pay for.

Merck spinoff Organon is at least one company bucking the trend. However, while the Jersey City-based venture is the largest biopharma company that focuses on women’s health, it’s far smaller than the majors.

When the company’s chief scientific officer Marcel van Duin was asked by Citi Global why there aren’t that many biopharma companies that have a similar focus on women, he replied “It’s more [financially] interesting for companies to be active in other therapeutic areas such as oncology … investors are of course looking at the return on their investments.”

According to a January report from the McKinsey Health Institute and the World Economic Forum, while women on average live longer than men, they spend 25% more of their lives in poor health and degrees of disability. That, in turn, affects her ability to be present and/or productive at home, in the workforce and in the community and reduces her earning potential.

Addressing that could not only improve the health and lives of millions of women, the report estimated it could boost by the global economy by at least $1 trillion annually by 2040.

Despite Bayer’s revised R&D strategy, the company said it seeks to raise the standard of care for menopausal women by broadening therapeutic options. Shortly after its March 2023 announcement about the company’s evolving research focus, Bayer affirmed its commitment to clinical-stage products, including elinzanetant.

At Bayer’s annual Pharma Media Day this past March in Berlin, Dr. Cecilia Caetano, the company’s head of global medical affairs and women’s health, said she believes the results from elinzanetant’s studies “are very encouraging to the many women worldwide suffering from vasomotor symptoms during their menopausal transition, which, along with sleep disturbances, are common symptoms which can strongly impact quality of life.”

“We are committed to advance science and break the silence by driving education, awareness and broadening treatment choices to support women across all stages of their lives,” she said.

Breaking the taboo

Until recently the health impacts of menopause have been largely ignored and dismissed for a variety of reasons, including negative stigmas, sex bias in research, lingering misinformation and insufficient funding.

Growing advocacy efforts are aimed at ending the silence around menopause and giving it the clinical – and cultural – attention the condition deserves.  That includes the Biden administration’s March announcement that the federal government will invest $200 million for research on women’s health care at the National Institutes of Health.

Celebrities, government officials and women with large social media platforms have also begun to speak publicly about their menopause symptoms, struggles and why they’re no longer willing to just grin and bear it.

For instance, earlier this month, actress Halle Berry screamed, “I’m in menopause!” at a media event on Capitol Hill to help unveil a $275 billion congressional bill to boost federal research, physician training and public awareness about menopause.

Last fall, actress Gwyneth Paltrow told People magazine she’s “in the thick” of perimenopause and that the years-long transition to menopause has been “quite a rollercoaster.” She also stressed the importance of simply talking about menopause because that may help women manage symptoms and understand that it’s a normal and natural process.

“For too long, vasomotor symptoms were written off as ‘par for the course’ for women as they age,” Abazia said. “And they were often just instructed to manage the symptoms with non-pharmacological methods: wear layers, buy fans, keep dry pajamas at the bedside … Modern society and the medical community no longer consider it reasonable for a woman to suffer two to 12 years.”

Abazia went on to point to growing research that links vasomotor symptoms with health risks, such as cardiovascular disease, depression and even cognitive decline.

“Modern [American] society is also accepting women’s health as an important area to devote resources and research dollars as the healthcare community moves away from the paternalistic view of medicine. And there are an increasing percentage of women moving into leadership roles within the pharmaceutical industry adding important voices as decision-maker to a historically male-dominated industry,” he stated.

Modern [American] society is also accepting women’s health as an important area to devote resources and research dollars as the healthcare community moves away from the paternalistic view of medicine.
– Daniel Abazia, Rutgers clinical associate professor

But it remains a taboo subject for many. Some women do not want to raise the issue in the doctor’s office, which has created an “invisible generation” of individuals suffering in silence through mentally and physically debilitating symptoms.  Research shows that only a minority of women today are receiving treatment and that many physicians are either untrained or uncomfortable when it comes to discussing menopause with their patients.

Additionally, most women don’t know the difference between menopause and perimenopause – the transitional years when declining estrogen levels can cause physical and emotional effects, like menstrual irregularities, night sweats, anxiety and mood swings.

Samantha Kleinberg, an associate professor in the Computer Science Department at Stevens Institute of Technology, told NJBIZ, “A majority of adults in the U.S. report not telling their doctors relevant information, mainly due to fear of judgment though also out of embarrassment. For menopause specifically, the vast majority of women report a sense of stigma, and many report feelings of shame and embarrassment.”

Kleinberg’s background includes researching how a patient’s decision to withhold information from their doctor can affect their treatment. Her research was not focused specifically on menopause but on medicine in general.

“I’ve found that unfortunately patients’ fears about judgment by doctors may be accurate. It is important for doctors to realize that patients may have important knowledge of their own health but are not experts and are seeking out doctors for their expertise. Doctors can help by sharing information proactively rather than waiting for patients to ask and working to build more mutual trust,” she said.