Bayer Launches Pivotal Phase III SUNFLOWER Trial to Evaluate Mirena® for the Treatment of Nonatypical Endometrial Hyperplasia
Bayer, a global pioneer in women’s healthcare, has officially initiated SUNFLOWER (Study of Understanding NAEH – treatment Efficacy of Levonorgestrel – IUS in Women Electing non-suRgical options), a pivotal Phase III clinical trial evaluating the use of its 52mg levonorgestrel-releasing intrauterine system (LNG-IUS), marketed as Mirena®, for the treatment of nonatypical endometrial hyperplasia (NAEH). This milestone marks a strategic expansion of Bayer’s robust clinical development program for intrauterine systems and underscores the company’s long-standing commitment to addressing critical gaps in women’s reproductive and gynecological health.
Understanding Nonatypical Endometrial Hyperplasia (NAEH)
Nonatypical endometrial hyperplasia is a benign but clinically significant condition characterized by abnormal thickening of the endometrium—the inner lining of the uterus—caused by prolonged exposure to unopposed estrogen without sufficient progesterone to balance it. Unlike its atypical counterpart, NAEH does not involve cellular changes that suggest precancerous development; however, it remains a serious condition due to its potential to progress to atypical hyperplasia or, ultimately, endometrial cancer if left untreated.
Symptoms of NAEH can be subtle or absent altogether, though many women experience abnormal uterine bleeding, including heavy menstrual periods, bleeding between cycles, or postmenopausal bleeding. These symptoms often prompt diagnostic evaluation, yet in some cases, NAEH is discovered incidentally during imaging or biopsy for unrelated issues.
Epidemiological data indicate that the annual incidence of NAEH varies widely depending on geographic region, age, and menopausal status, ranging from 121 to 270 cases per 100,000 women. The condition is more prevalent among women in perimenopause or early postmenopause, those with obesity, polycystic ovary syndrome (PCOS), or other conditions that disrupt hormonal balance. Given its prevalence and potential for malignant transformation, timely and effective management is essential.
A Critical Gap in Treatment Options
Despite its clinical relevance, NAEH currently lacks an approved medical therapy. Standard approaches often involve close monitoring, lifestyle modifications (such as weight loss), or—when progression is a concern—surgical intervention, including hysterectomy. While progestin-based therapies have been used off-label in clinical practice to counteract estrogen-driven endometrial proliferation, none have received formal regulatory approval specifically for NAEH.
This absence of an approved pharmacologic option represents a substantial unmet medical need, particularly for women who wish to avoid surgery, preserve fertility, or seek long-term, reversible management. It is within this context that Bayer’s SUNFLOWER trial assumes critical importance.
Mirena®: A Proven Platform with Expanding Therapeutic Potential
Mirena® (52mg LNG-IUS) is a well-established, long-acting, reversible contraceptive device that has been available globally for over two decades. Beyond contraception, it is approved in more than 120 countries for several gynecological indications, including the treatment of heavy menstrual bleeding (HMB), endometrial protection in women undergoing estrogen-only hormone replacement therapy for menopausal symptoms, and the management of menstrual pain (dysmenorrhea).
The 52mg LNG-IUS works by locally releasing levonorgestrel—a potent progestin—directly into the uterine cavity. This localized delivery achieves high endometrial concentrations while minimizing systemic exposure, thereby offering effective endometrial suppression with a favorable safety profile. Its mechanism of action makes it biologically plausible for use in estrogen-driven endometrial conditions like NAEH, where progestogenic counterbalance is therapeutically essential.
The SUNFLOWER Trial: Design and Significance
The SUNFLOWER trial is a multicenter, randomized, open-label Phase III study designed to rigorously evaluate the efficacy and safety of the 52mg LNG-IUS in women diagnosed with NAEH who opt for non-surgical management. The primary endpoint will assess histological regression of endometrial hyperplasia at 6 months following device insertion, with secondary endpoints including long-term disease control, safety, tolerability, quality-of-life measures, and patient-reported outcomes.
By enrolling a diverse, global cohort of patients, SUNFLOWER aims to generate high-quality evidence that could support regulatory submissions for a new indication for Mirena®—potentially making it the first and only approved medical therapy for NAEH worldwide. If successful, this would represent a paradigm shift in clinical practice, offering millions of women a safe, effective, and reversible alternative to watchful waiting or invasive procedures.
A Strategic Step in Bayer’s Women’s Health Vision
Christian Rommel, Ph.D., Head of Research and Development at Bayer’s Pharmaceuticals Division, emphasized the strategic and humanitarian motivations behind the trial: “Having a leading position in global women’s health, we are committed to advancing science with a focus on innovative options that address the unmet medical needs of women worldwide. With this new Phase III study, we are expanding our broad clinical development program for intrauterine systems to support women suffering from nonatypical endometrial hyperplasia with an effective, non-surgical treatment option.”
This initiative aligns with Bayer’s broader mission to champion women’s health across the lifespan—from reproductive years through menopause and beyond. The company has consistently invested in research on hormonal and non-hormonal solutions for gynecological conditions, recognizing that many such disorders remain underdiagnosed, undertreated, or stigmatized.
Addressing a Global Health Priority
Endometrial disorders, including hyperplasia and cancer, are rising in incidence worldwide, driven in part by increasing rates of obesity, metabolic syndrome, and delayed childbearing. In low- and middle-income countries, where access to specialized gynecological care and surgical options may be limited, a simple, long-acting, office-based intervention like the LNG-IUS could dramatically improve health outcomes and reduce disparities in care.
Moreover, by offering a fertility-sparing option, Mirena® could be particularly valuable for younger women diagnosed with NAEH who may still desire future pregnancies. Current management strategies often lack clarity for this demographic, and an approved therapy would provide much-needed clinical guidance and patient empowerment.
Building on a Legacy of Innovation
Mirena®’s journey from a contraceptive device to a multifaceted therapeutic tool exemplifies Bayer’s commitment to lifecycle innovation. Since its initial approval, clinical research has progressively uncovered additional benefits of the LNG-IUS, leading to expanded indications that reflect real-world patient needs. The SUNFLOWER trial continues this legacy, leveraging decades of safety data and clinical experience to explore new frontiers in endometrial health.
Regulatory agencies, including the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA), have historically recognized the value of repurposing well-characterized medical devices for novel indications when supported by robust evidence. Should SUNFLOWER meet its endpoints, Bayer is well-positioned to engage with health authorities globally to seek approval for this new use.
About SUNFLOWER study
The Phase III clinical study SUNFLOWER (Study ofUnderstandingNAEH – treatmenteFficacy ofLevonOrgestrel – IUS inWomenElectingnon-suRgical options) will evaluate the treatment of nonatypical endometrial hyperplasia (NAEH) with 52mg LNG IUS versus Oral Progestin (OP) and aims to enroll 207 patients at about 90 centers in 3 countries. The study is anticipated to take around 1.5 years until completion.
Previous studies4,5,6 that have tested the use of 52mg LNG-IUS for the treatment of this condition indicate good response based on the type of hormone present in the IUS and the direct effect inside the uterus, helping to bring the endometrium back to normal state in most cases. The aim of SUNFLOWER is to assess how 52mg LNG-IUS is treating NAEH in a controlled clinical study.
About Mirena®
Mirena is a T-shaped device containing 52 mg of synthetic levonorgestrel. Once placed in the uterus, it continuously releases small amounts of levonorgestrel directly into the uterus. Mirena is a long-acting reversible contraceptive (LARC) and can be removed at any time by a healthcare provider if a woman’s plans change. The current approved indications which may vary from country to country are contraception (prevention of pregnancy), idiopathic menorrhagia/ heavy menstrual bleeding (HMB), endometrial protection during estrogen therapy for menopause and dysmenorrhea (painful periods). Mirena is available in more than 120 countries.
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 2024, the Group employed around 93,000 people and had sales of 46.6 billion euros. R&D expenses amounted to 6.2 billion euros. For more information, go to www.bayer.com.
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