Endometrial Hyperplasia

Bayer touted more detailed data from a Phase 3 trial for elinzanetant, a non-hormonal drug candidate that it’s investigating as a treatment for menopause symptoms like hot flashes and night sweats. The OASIS 3 trial hit the primary endpoint of demonstrating a statistically significant reduction in the frequency of moderate to severe vasomotor symptoms from baseline to week 12 compared to placebo, according to results set to be presented Tuesday at The Menopause Society’s annual meeting in Chicago. After 12 weeks of treatment, the number of vasomotor symptoms was reduced to 1.6 in the elinzanetant group and 3.4 in the placebo group, with the reductions in symptoms maintained throughout the 52-week study. Patients on Bayer’s drug self-reported improvements in sleep as well. Based on positive results from this trial and two other late-stage studies called OASIS 1 and 2 , Bayer submitted an NDA to the FDA for elinzanetant in August, and it plans to file applications to other regulatory agencies. The company told investors this summer that it’s aiming to launch the drug in 2025. Bayer first released topline data for OASIS 3 in March. The most common treatment-emergent adverse events in the elinzanetant arm were headaches and Covid-19, and Bayer noted there were no signs of liver toxicity or incidences of endometrial hyperplasia or endometrial malignant neoplasms. James Simon, study author and clinical professor of obstetrics and gynecology at George Washington University in Washington, DC, told Endpoints News that longer-term studies like OASIS 3 are “really, really important,” especially for this drug class. Elinzanetant is a dual neurokinin-1 and -3 receptor antagonist, which Bayer says is the first drug of its kind in late-stage development for the treatment of menopausal vasomotor symptoms associated with menopause. It’s given orally once a day. “In this particular case, safety has been brought more to the forefront, because drugs in this class, the neurokinin modulators, some of them have failed and been very problematic for safety, and have never really come to become clinically tested,” Simon said. “Others already on the market have some minor or mild safety signals, which have elevated the FDA to make changes in and restrictions in their labeling that are safety-related.” JoAnn Pinkerton, the study’s author and division director of Midlife Health Center at UVA Health in Charlottesville, VA, said that Bayer’s drug could be a new treatment option for menopausal women with these symptoms who can’t or don’t want to take hormone therapies. She also noted that another ongoing Phase 3 trial called OASIS 4 is investigating the drug in women who either are at high risk for breast cancer or who have had breast cancer. These patients are also on a therapy and endocrine therapy either to prevent or treat breast cancer. “When you look at the populations of women who can’t take hormone therapy or choose not to, it’s women that are at risk for breast cancer, or have had breast cancer, stroke or blood clots, migraines. Those are women that need help, and we haven’t had effective treatment to date,” Pinkerton said.

Bayer has unveiled detailed data from two pivotal trials of its investigational menopause drug elinzanetant, setting the stage for a heated commercial battle with Astellas' already approved Veozah (fezolinetant) in the long-neglected vasomotor symptoms (VMS) market.At the American College of Obstetricians and Gynecologists (ACOG) annual meeting, Bayer presented detailed results from the OASIS 1 and 2 studies, demonstrating that the dual neurokinin-1,3 (NK-1,3) receptor antagonist significantly reduced the frequency and severity of moderate-to-severe hot flashes associated with menopause. A total of about 800 post-menopausal women were enrolled across the two studies.Stacking up to VeozahIn OASIS 1, elinzanetant showed significant mean reductions versus placebo in hot flash frequency of 3.29 at week 4 and 3.22 at week 12. For severity, the reductions were 0.33 and 0.40 at those timepoints, respectively.OASIS 2 yielded similar results, with elinzanetant demonstrating significant mean reductions in frequency of 3.04 at week 4 and 3.24 at week 12, and in severity of 0.22 and 0.29, respectively.The data could position elinzanetant as a strong competitor to Veozah, an NK-3 receptor antagonist approved last year for the treatment of VMS. It is also cleared in Europe under the name Veoza. In the SKYLIGHT 1 and SKYLIGHT 2 trials, Astellas' drug reduced hot flash frequency by 2.07 and 2.55 at week 4 and by 2.53 and 2.55 at week 12. Hot flash severity reductions were about 0.20 and 0.29 across the two SKYLIGHT studies, respectively.While efficacy data suggest a closely matched rivalry, other factors could tilt the scales. Bayer said elinzanetant also met key secondary endpoints in OASIS 1 and 2, significantly improving sleep compared to placebo. Mean change from baseline to week 12 on the PROMIS sleep disturbance measure was 5.58 in OASIS 1 and 4.32 in OSAIS 2 in favour of elinzanetant over placebo.No liver injuryStudy drop-outs due to adverse events were higher in the elinzanetant arms than placebo in both studies (8.5% vs 6.7% in OASIS 1; 6.5% vs 2% in OASIS 2).Liver safety has also been a point of concern for Veozah, which requires liver function testing due to possible increases in hepatic serum transaminase levels. However, researchers said there were "no cases of drug-induced liver injury causally related to elinzanetant" or any incidences of endometrial hyperplasia or malignant neoplasm in either of the OASIS studies, according to the ACOG presentations.In a recent interview with FirstWord, Waljit Dhillo, professor of endocrinology and metabolism at Imperial College London, said "it would definitely be a big difference" if elinzanetant avoids such liver monitoring requirements. "If you can just give a tablet and then go away, that would be attractive."Hitting the NK1 receptor could theoretically provide elinzanetant with better liver safety and less sleep disturbance compared to Veozah, which only targets NK3. However, when asked how optimistic he was about whether elinzanetant could necessitate less liver monitoring, Dhillo noted that since there are no NK3 receptors in the liver, any differentiation in liver safety may come down to differences in the specific molecules rather than their receptor targets.FirstWord recently caught up with Astellas leadership to discuss Veozah, including the concerns regarding liver safety. For more on that interview, see – ViewPoints: Having broken ground in untapped menopause market, Astellas outlines strategy for Veozah as competition heats up.First-mover advantage?"The robust efficacy and favourable safety profile of elinzanetant reinforces its potential as a non-hormonal treatment for women experiencing menopause," said Bayer's R&D head Christian Rommel in a company release. Bayer plans to submit elinzanetant's data to regulatory authorities for marketing approval this year, setting up a commercial clash with Astellas' first-mover advantage. "Our preparations to obtain first-market authorisations are running at full steam," Bayer CEO Bill Anderson stated at the company's earning call this week.Bayer would not disclose elinzanetant's price until the FDA clears it, although some analysts suggest it could cost as much as or more than Veozah, which can cost at least $550 for a month's supply.Commenting on the OASIS readouts, Morgan Stanley analysts said that "although elinzanetant appears slightly more effective than Veozah in reducing symptom frequency over 12 weeks, we do not think this will make a big difference in terms of business. Bayer is due to launch the drug in 2025, giving Veozah a two-year advantage."

Detailed results from pivotal Phase III studies OASIS 1 and 2 evaluating the efficacy and safety of investigational compound elinzanetant will be presented for the first time at this year’s American College of Obstetricians and Gynecologists (ACOG) Elinzanetant is a first dual neurokinin-1,3 (NK-1,3) receptor antagonist being studied for the non-hormonal treatment of moderate to severe VMS associated with menopause, administered orally once daily Additional presentations include a variety of posters and oral presentations that span across Bayer’s contraception and menopause portfolio as well as two scientific symposia Presentations demonstrate Bayer’s long-standing commitment in women’s healthcare as the company continues to address relevant unmet medical needs for women BERLIN--(BUSINESS WIRE)-- Bayer will present detailed results from the pivotal Phase III studies OASIS 1 and 2, evaluating the efficacy and safety of the investigational compound elinzanetant versus placebo, at the upcoming American College of Obstetricians and Gynecologists (ACOG) Annual Clinical & Scientific Meeting. ACOG takes place from May 17 – 19, in San Francisco, CA, United States. Additional presentations will feature new findings from Bayer’s intrauterine systems (IUS) and menopause product portfolio, as well as a scientific symposium session on the science behind menopause symptoms. These presentations demonstrate Bayer’s long-standing commitment to advance women’s healthcare as the company works towards broadening treatment options for women. OASIS 1 and 2 data presentations: Scientific Symposium: OASIS 1 and 2: Elinzanetant Efficacy and Safety Data From 2 Pivotal Studies James A. Simon, MD and JoAnn V. Pinkerton, MD Friday, 17 May, 5:15 – 6:00 PM PST, Location: 154 E-Poster #IP05-C: First Phase 3 trial evaluating the efficacy and safety of elinzanetant for the treatment of vasomotor symptoms associated with menopause (OASIS 2) JoAnn V. Pinkerton, MD Saturday, 18 May, 9:30 – 10:30 AM PST, Location: Hall C E-Poster #IP05-D: Second Phase 3 trial OASIS 1 confirms efficacy and safety of elinzanetant for the treatment of vasomotor symptoms associated with menopause James A. Simon, MD Saturday, 18 May, 09:30 – 10:30 AM PST, Location: Hall C Additional Bayer presentations include: Scientific Symposium: Understanding Menopause: The Science Behind the Symptoms JoAnn V. Pinkerton, MD and Victor Navarro, MD Saturday, 18 May, 7:00 – 7:45 AM PST, Location: 153 E-Poster #IP01-A: LNG-IUS for the Treatment of Endometrial Hyperplasia and Early-stage Endometrial Cancer: a Systematic Review and Meta-analysis Kristina Rosa Cruz Bolling, PhD Friday, 17 May, 10:30 – 11:30 AM PST, Location: Hall C E-Poster #IP01-B: Treatment and clinical characteristics of perimenopausal and menopausal women with vasomotor symptoms (VMS): a real-world data analysis Lena Charafi, DPharm Friday, 17 May, 10:30 – 11:30 AM PST, Location: Hall C About the OASIS 1, 2 and 3 studies OASIS 1 and 2 are double-blind, randomized, placebo-controlled multicenter studies investigating the efficacy and safety of elinzanetant administered orally once daily in women with moderate to severe VMS associated with menopause over 26 weeks. OASIS 1 and 2 randomized 396 and 400 postmenopausal women between 40 and 65 years across 184 sites in 15 countries. OASIS 3 is a double-blind, randomized, placebo-controlled multicenter study to investigate the efficacy and safety of elinzanetant for the treatment of vasomotor symptoms over 52 weeks in postmenopausal women. OASIS 3 randomized 628 postmenopausal women between 40 and 65 years across 83 sites in 9 countries. Bayer will submit the data from the OASIS 1, 2 and 3 studies to health authorities for approval of marketing authorizations of elinzanetant for the treatment of moderate to severe VMS associated with menopause. About the Elinzanetant Clinical Development Program The Phase III clinical development program of elinzanetant, OASIS, currently comprises four Phase III studies: OASIS 1, 2, 3 and 4. The OASIS 1, 2 and 3 studies investigate the efficacy and safety of elinzanetant 120 mg in women with moderate to severe VMS associated with menopause. The OASIS 4 study is an expansion of the clinical Phase III program and investigates the efficacy and safety of elinzanetant in women with moderate to severe VMS caused by endocrine therapy for treatment or prevention of breast cancer. The design and dosing of the Phase III clinical development program is based on the positive data from two Phase II studies (RELENT-1 and SWITCH-1). RELENT-1 was a Phase Ib/IIa study investigating the safety, pharmacokinetics and preliminary efficacy of elinzanetant. SWITCH-1 was a Phase IIb study investigating the efficacy and safety of four different doses of elinzanetant compared to placebo in women with VMS. In addition to the OASIS program, Bayer started NIRVANA (NCT06112756), an exploratory Phase II randomized, parallel-group treatment, double-blind study. The primary objective is to explore the efficacy of elinzanetant on sleep disturbances associated with menopause as determined by polysomnography (PSG). PSG is a validated method to study sleep and underlying causes of sleep disturbances. Additional objectives include exploring the efficacy of elinzanetant on SDM as determined by patient-reported outcomes and further evaluating the safety of elinzanetant. About Elinzanetant Elinzanetant is the first dual neurokinin-1,3 (NK-1,3) receptor antagonist in late-stage clinical development for the non-hormonal treatment of moderate to severe VMS associated with menopause, administered orally once daily. Elinzanetant may address moderate to severe VMS by modulating a group of estrogen sensitive neurons in the hypothalamus region of the brain (the KNDy neurons) which, with the decrease of estrogen, become hypertrophic and lead to a hyperactivation of the thermoregulatory pathway, consequently disrupting body heat control mechanisms resulting in VMS. Elinzanetant may also decrease sleep disturbances associated with menopause. About Vasomotor Symptoms Vasomotor symptoms (VMS; also referred to as hot flashes) result from hyperactivation of the thermoregulatory pathway mediated by hypertrophy of the KNDy neurons. This is due to a decrease of estrogen, which can result from the progressive reduction of ovarian function due to natural menopause or medical intervention by bilateral oophorectomy or endocrine therapy. VMS are reported by up to 80% of women at some point during the menopausal transition and are one of the leading causes for seeking medical attention during this phase of a woman’s life. Over one-third of menopausal women report severe symptoms, which can last 10 years or more after the last menstrual period, with relevant impact on quality of life. VMS may also be caused by endocrine therapy, for the treatment or prevention of breast cancer, impacting quality of life and treatment adherence. For these women, there are currently no approved treatment options. About Menopause By 2030, the global population of women experiencing menopause is projected to increase to 1.2 billion, with 47 million women entering this phase each year. Menopause is a transitional phase in women’s lives, related to the progressive decline of ovarian function. It usually occurs in women during their 40s or early 50s. It can also be the result of surgical or medical treatment such as breast cancer treatment. The hormonal decline can lead to various symptoms which can substantially affect a woman’s health, quality of life, healthcare utilization and work productivity. The most frequently reported and disruptive symptoms during the menopausal transition are VMS, sleep disturbances and mood changes. Addressing these symptoms is key to maintaining functional ability and quality of life in menopause which is highly relevant from both a healthcare and socio-economic perspective. About Women’s Healthcare at Bayer Women’s Health is in Bayer’s DNA. As a global leader in women’s healthcare Bayer has a long-standing commitment to delivering science for a better life by advancing a portfolio of innovative treatments. Bayer offers a wide range of effective short- and long-acting birth control methods as well as therapies for menopause management and gynecological diseases. Bayer is also focusing on innovative options to address the unmet medical needs of women worldwide and to broadening treatment choices such as in menopause. Additionally, Bayer intends to provide 100 million women per year in low-and-middle income countries by 2030 with access to family planning by funding multi-stakeholder aid programs for capacity building and by ensuring the supply of affordable modern contraceptives. This is part of the comprehensive sustainability measures and commitments from 2020 onwards and in line with the Sustainable Development Goals of the United Nations. About Bayer Bayer is a global enterprise with core competencies in the life science fields of health care and nutrition. In line with its mission, “Health for all, Hunger for none,” the company’s products and services are designed to help people and the planet thrive by supporting efforts to master the major challenges presented by a growing and aging global population. Bayer is committed to driving sustainable development and generating a positive impact with its businesses. At the same time, the Group aims to increase its earning power and create value through innovation and growth. The Bayer brand stands for trust, reliability and quality throughout the world. In fiscal 2023, the Group employed around 100,000 people and had sales of 47.6 billion euros. R&D expenses before special items amounted to 5.8 billion euros. For more information, go to . Find more information at Follow us on Facebook: Follow us on Twitter: @BayerPharma kw (2024-0065E) Forward-Looking Statements This release may contain forward-looking statements based on current assumptions and forecasts made by Bayer management. Various known and unknown risks, uncertainties and other factors could lead to material differences between the actual future results, financial situation, development or performance of the company and the estimates given here. These factors include those discussed in Bayer’s public reports which are available on the Bayer website at . The company assumes no liability whatsoever to update these forward-looking statements or to conform them to future events or developments.