Elinzanetant Meets All Endpoints in Phase 3 Study of VMS Caused by Adjuvant Endocrine Therapy for Breast Cancer
Elinzanetant produced a statistically significant reduction in frequency of treatment-related vasomotor symptoms as early as week 1 and in severity at weeks 4 and 12.
Elinzanetant, an investigational dual neurokinin-1 and 3 (NK-1,3) receptor antagonist, has demonstrated significant efficacy and safety in the phase III OASIS 4 trial, according to topline results announced by Bayer on January 9, 2025. The study evaluated the non-hormonal treatment’s ability to alleviate moderate to severe vasomotor symptoms (VMS) in women undergoing adjuvant endocrine therapy for hormone receptor-positive breast cancer or those at high risk of developing the disease.
Prof Fatima Cardoso, MD
Courtesy of Champalimaud Foundation
The trial, conducted at 90 centers in 16 countries outside the US, met all primary and secondary endpoints, according to Bayer’s announcement. Elinzanetant achieved a statistically significant reduction in the frequency of moderate to severe VMS from baseline to weeks 4 and 12 compared to placebo. Notably, the treatment’s effects were observed as early as week 1 and sustained over the 52-week study period, Bayer said. Additional benefits included reductions in VMS severity and improvements in sleep disturbances and menopause-related quality of life. The safety profile of elinzanetant over 52 weeks was consistent with data from prior studies in postmenopausal women.
“For women undergoing endocrine therapy, managing menopausal symptoms like VMS is essential for maintaining adherence to life-saving treatments,” Fatima Cardoso, MD, OASIS 4 principal investigator and Director of the Breast Unit of the Champalimaud Clincal Centre in Lisbon, Portugal, said in the statement. “The promising results of this study bring us closer to a much-needed therapeutic option.”
“Elinzanetant has consistently demonstrated positive outcomes across all four phase III trials in the OASIS program,” Christian Rommel, head of research and development at Bayer’s Pharmaceuticals Division, noted in the press statement. “The results from OASIS 4 address a significant unmet medical need, offering a potential non-hormonal treatment for VMS in women affected by or at high risk for breast cancer.”
Elinzanetant is currently under review by the FDA for management of moderate-to-severe VMS associated with menopause. In October the agency set a Prescription Drug User Fee Act target date for July 26, 2025.2
Unmet Need
VMS, commonly known as hot flashes, are a frequent adverse effect of adjuvant endocrine therapies such as tamoxifen or aromatase inhibitors. These therapies, crucial for reducing breast cancer recurrence and mortality, are often prescribed for up to 10 years. However, the associated VMS can significantly impact quality of life and treatment adherence, potentially influencing long-term outcomes.
Approximately 70% of breast tumors are hormone receptor-positive, making adjuvant endocrine therapy a standard recommendation for patients. For women experiencing VMS related to these treatments, no approved non-hormonal options currently exist, highlighting the importance of the OASIS 4 findings.
OASIS 4
The OASIS 4 double-blind, randomized, placebo-controlled trial is the first pivotal international phase 3 study to address the needs of women with, or at high risk for developing hormone-receptor positive breast cancer, Bayer noted. Among 474 participants randomly assigned to receive a 120 mg oral dose of elinzanetant or placebo, the study investigated the efficacy and safety of the novel treatment over 52 weeks, with an optional extension of up to 2 years.
Primary outcomes included reductions in the frequency of moderate to severe VMS at weeks 4 and 12, while secondary outcomes assessed improvements in symptom severity, sleep disturbances, and menopause-related quality of life. The rapid onset of efficacy, seen as early as week 1, and the maintenance of benefits over the study period underscore the potential of elinzanetant as a long-term treatment.
Novel Mechanism of Action
Elinzanetant is the first dual NK-1,3 receptor antagonist and modulates the activity of KNDy neurons in the hypothalamus, which become hyperactive due to reduced estrogen levels during menopause or endocrine therapy. This hyperactivation disrupts thermoregulation, leading to VMS.
The OASIS program includes four Phase III trials, each reinforcing the safety and efficacy profile of elinzanetant. Data from OASIS 1 and 2, published in JAMA in August 2024, and results from OASIS 3, presented at The Menopause Society annual meeting in September 2024, further validate these findings.
Bayer is pursuing regulatory submissions for elinzanetant in the United States, European Union, and other global markets. Detailed results from OASIS 4 will be presented at upcoming scientific congresses, providing further insights into its potential role in addressing VMS caused by adjuvant endocrine therapy.
