The Journal of American Medical Association (JAMA) publishes elinzanetant phase III data.- Bayer.

This data reinforces the strong evidence of efficacy and safety of the compound. Elinzanetant is the first dual neurokinin-1 and 3 (NK-1 and 3) receptor antagonist in late-stage clinical development for the non-hormonal treatment of moderate to severe vasomotor symptoms (VMS) associated with menopause, administered orally once daily.

Elinzanetant met all primary endpoints in the OASIS 1 and 2 studies, significantly reducing frequency and severity of moderate to severe VMS associated with menopause compared to placebo at weeks 4 and 12. In addition, elinzanetant met all key secondary endpoints showing a statistically significant reduction in the frequency of VMS from baseline to week 1 and statistically significant improvement of sleep disturbances and menopause related quality of life, compared to placebo.

In the OASIS 1 study, the frequency of VMS was reduced by 55.9% from baseline to week 4 and 65.2% to week 12, compared to reductions of 31.4% and 42.2% respectively for placebo. In the OASIS 2 study, similar results were seen with a reduction of 57.9% to week 4 and 67.0% to week 12, compared to reductions of 35.7% and 45.9% respectively in the placebo group.

By week 26, over 80% of participants had achieved at least a 50% reduction in VMS frequency in the elinzanetant group (81.6% and 81.5% in OASIS 1 and 2 respectively) and in those who switched from placebo to elinzanetant after week 12 (84.5% and 86.7% in OASIS 1 and 2 respectively). In addition, a statistically significant reduction was seen for VMS severity from baseline to weeks 4 and 12 with elinzanetant compared to placebo. In both studies elinzanetant showed a rapid onset of action as early as week 1 with statistically significant reduction in the frequency of VMS from baseline.

"Due to individual risk factors, medical contraindications or personal preference, there is an unmet need for additional safe and effective non-hormonal treatments for vasomotor symptoms associated with menopause that may also improve sleep disturbances and quality of life,” said JoAnn Pinkerton, M.D., Professor and Director of Midlife Health at UVA Health. “These positive results from OASIS 1 and 2 reinforce elinzanetant as a potential non-hormonal treatment option for women experiencing vasomotor symptoms in menopause.”

By meeting one of the key secondary endpoints, elinzanetant demonstrated significant reductions in sleep disturbances across both OASIS 1 and 2 studies. At baseline, participants on average experienced moderate sleep disturbances, highlighting the prevalence of this symptom for menopausal women. Following treatment with elinzanetant, the average scores were reduced to the normal range while scores in the placebo group fell within the mild sleep disturbance range. The range of normal, mild and moderate sleep disturbances is according to classification in a reference population. These data reinforce that elinzanetant, as a dual NK-1 and 3 receptor antagonist, has the potential to improve sleep disturbances in menopausal women. Additionally, elinzanetant also improved menopause-related quality of life showing statistical significance compared to placebo.

Furthermore, reductions in frequency and severity of VMS as well as the improvements in sleep disturbances and menopause-related quality of life were maintained throughout the 26-week treatment period in the elinzanetant group. Improvements in these measures were similarly observed in the group that switched from placebo to elinzanetant after week 12.

“Women experiencing menopause need treatment options that can help reduce the impact of symptoms on their quality of life,” said James A. Simon, M.D., Clinical Professor of Obstetrics and Gynecology at George Washington University. “The results from OASIS 1 and 2 are very promising when looking to address the unmet needs many women may experience during the menopause transition.”

The safety profile of elinzanetant was favorable in both studies with headache and fatigue being the most frequently reported treatment emergent adverse events (TEAEs) within the elinzanetant groups. No liver toxicity was observed in the two studies. Additional safety data will be available from the 52-week placebo-controlled OASIS 3 Phase III study evaluating the efficacy and long-term safety of elinzanetant versus placebo, which Bayer announced positive topline results earlier this year.

Bayer has submitted a New Drug Application to the FDA for elinzanetant for the treatment of moderate to severe VMS associated with menopause based on positive results data from the OASIS 1, 2 and 3 studies. Bayer will submit applications for marketing authorizations of elinzanetant to additional health authorities as well.

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.

In addition to the OASIS program, Bayer is conducting 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.

See-"Elinzanetant for the Treatment of Vasomotor Symptoms Associated With Menopause: OASIS 1 and 2 Randomized Clinical Trials"- JoAnn V. Pinkerton, MD, MSCP; James A. Simon, MD, MSCP; Hadine Joffe, MD, MSc; Pauline M. Maki, PhD; Rossella E. Nappi, MD, PhD; Nick Panay, BSc, MBBS; Claudio N. Soares, MD, PhD, MBA; Rebecca C. Thurston, PhD; Cecilia Caetano, MD; Claudia Haberland, PhD; Nazanin Haseli Mashhadi, MSc(Statistics); Ulrike Krahn, PhD; Uwe Mellinger, Dipl-Math; Susanne Parke, MD; Christian Seitz, MD; Lineke Zuurman, MD, PhD.JAMA. 2024; 10.1001/jama.2024.14618.