George L. Maxwell, MD, discusses phase 3 SUNFLOWER trial to evaluate Mirena for nonatypical endometrial hyperplasia

Bayer recently announced the initiation of SUNFLOWER, a phase 3 study evaluating the efficacy and safety of the 52-mg levonorgestrel-releasing intrauterine system (Mirena) for nonatypical endometrial hyperplasia (NAEH). Approximately 121 in 100,000 women develop NAEH annually, and no FDA-approved medical treatments currently exist. The condition represents benign endometrial thickening and may result in heavy bleeding, abnormal bleeding, or postmenopausal bleeding. If untreated, NAEH may progress to uterine cancer.

George L. Maxwell, MD, president of women’s services for the Inova Health System and a gynecologic oncologist, emphasized the clinical need. “We don't have any medically or FDA-approved medical intervention for the treatment of non-atypical endometrial hyperplasia,” he said. “There's probably around 10% of these lesions that have unchecked or untreated can progress to cancer.”

Mirena is approved in the United States for pregnancy prevention for up to 8 years and for treatment of heavy menstrual bleeding for up to 5 years in women choosing intrauterine contraception, but is not approved for treatment of NAEH.

Mirena mechanism, progestin delivery, and treatment rationale

The SUNFLOWER study builds on observational data suggesting benefit from intrauterine levonorgestrel. Maxwell stated, “It has shown effect in treatment of hyperplasia and even more advanced atypical forms, even early endometrial cancers, observational.”

He noted the therapeutic rationale for local progestin delivery. “The delivery of the progestin and immediate proximity endometrium enables us to deliver high doses to the endometrium and potentially avoid some of the side effects that might be associated with taking oral, systemic progestins,” he said.

Maxwell also noted that previous studies suggest intrauterine levonorgestrel may restore the endometrium to its normal state.

Study endpoints for Mirena vs oral progestin in NAEH

The primary endpoint of the study is lesion resolution after 6 months. “The primary outcome, our aim of the study is to look for resolution of these lesions after six months of treatment,” Maxwell explained.

Secondary endpoints include recurrence, progression, need for hysterectomy, and adverse events. Investigators will also monitor recurrence after a 3-month observational period following treatment discontinuation. Maxwell noted, “We're really going to be looking at resolution, progression, side effects, recurrence… for the effectiveness of the two study drugs.”

SUNFLOWER will compare Mirena with an oral progestin and is expected to enroll approximately 207 patients across about 90 centers in the United States, Canada, and China.

SUNFLOWER trial design, enrollment plans, and global reach

Maxwell described the broad scope of the study. “I have to commend Bayer in taking on an ambitious trial that is going to be in over 90 sites,” he said. Early US enrollment has begun.

He added that the multinational footprint “enables us to not only cover multiple populations, but socioeconomic strata and even geographical, international generalizability of our findings.” Enrollment completion is expected next summer, with final follow-up anticipated in spring 2027.

Potential clinical impact and future research directions

Maxwell noted that a medical indication could expand access. “It enables us to potentially look at non-invasive options of treatment for patients across all socioeconomic strata,” he stated.

He explained that findings may support future research in atypical hyperplasia and chemoprevention. “Ultimately, I think this is the first step in a journey to being in that space,” he said.

He emphasized the importance of the trial: “It is an unmet need and a problem that continues to escalate… the data we gain from this trial have great generalizability across populations… and it will definitely give us information to inform potential future trials to follow.”

Disclosure

Maxwell is the co-principal investigator for the phase 3 SUNFLOWER trial.

Reference

Bayer. Bayer Starts New Phase III Study with Mirena® for the Treatment of Nonatypical Endometrial Hyperplasia. Businesswire. December 2, 2025. Accessed December 10, 2025. https://www.businesswire.com/news/home/20251202439858/en/Bayer-Starts-New-Phase-III-Study-with-Mirena-for-the-Treatment-of-Nonatypical-Endometrial-Hyperplasia