Elinzanetant displays positive phase 3 safety and efficacy data against VMS

In a recent phase 3 randomized trial presented at the 2024 Annual Meeting of The Menopause Society, elinzanetant displayed positive safety and efficacy data for the treatment of moderate-to-severe vasomotor symptoms (VMS).¹

Additional safe and effective nonhormone treatments are needed for the treatment of VMS, defined as bothersome menopausal symptoms adversely impacting women’s quality of life. In the OASIS phase 3 randomized, double-blind clinical trial, the safety and efficacy of elinzanetant was evaluated against moderate-to-severe VMS.

Participants included naturally or surgically postmenopausal women aged 40 to 65 years with moderate-to-severe VMS. These patients were randomized 1:1 to receive either elinzanetant 120 mg or placebo. Treatment lasted for 52 weeks and was administered orally once per day.

The mean change in the frequency of moderate-to-severe VMS from baseline to week 12 was reported as the primary outcome of the analysis, measured using the Hot Flash Daily Diary. Secondary endpoints included the mean changes in Patient-Reported Outcomes Measurement Information System Sleep Disturbance Short Form (PROMIS SD SF) and Menopause-Specific Quality of Life (MENQOL) scores.

Safety was determined based on treatment-emergent adverse events (TEAEs), bone mineral density (BMD), endometrial biopsies, weight, and laboratory parameters. Drug-induced liver injury was assessed using based on predefined criteria for close liver observation (CLO).

A mixed model with repeated measures was used to evaluate the primary endpoint, with treatment interruptions managed through a treatment policy strategy. All other analyses were descriptive.

Participants were aged a mean 54.6 years in the elinzanetant group and 54.9 years in the placebo group. White race was reported in 76.7% and 80.3%, respectively, and both groups had a mean body mass index of 27.6.

In the elinzanetant group, a mean 1.6 moderate-to-severe VMS per day were recorded at week 12, vs 3.4 in the placebo group. This indicated a least-square mean difference of -1.6 VMS per day.

For PROMIS SD SF scores, a mean change of -9.4 was reported from baseline to week 52 in the elinzanetant group vs -5.7 in the placebo group. Changes in MENQOL total scores were -1.3 and -1.1, respectively.

In terms of safety outcomes, neither group reported a case of endometrial hyperplasia or malignant neoplasm. Additionally, BMD changes between baseline and week 52 were within expected age-related loss in both groups, and both groups maintained stable weight.

There were 10 cases of fulfilled CLO criteria reported, 6 in the elinzanetant group and 4 in the placebo group. No indications of cholestatic injury were identified.

These results indicated positive safety and efficacy results from elinzanetant for the treatment of moderate-to-severe VMS. This data supports the results of the OASIS 1 and 2 trials, highlighting efficacy over a longer study duration.

In an interview with Contemporary OB/GYN at the 2024 Annual Meeting of The Menopause Society, JoAnn Pinkerton, MD, FACOG, NCMP, discussed the results of the OASIS 3 trial.²

"The good news was that Oasis we met its primary objective," Pinkerton said. "Hot flushes were significantly reduced at 12 weeks in this population of women who were not as severe as those in OASIS 1 and 2—more like you would see in your clinical practice—significantly reduced compared to placebo at 12 weeks, and then maintained that efficacy throughout the 52 weeks.”

More of our discussion with Pinkerton can be watched below.

References

1. Panay N, Joffe H, Maki P, et al. Efficacy and long-term safety of elinzanetant for the treatment of VMS associated with menopause:A phase 3 randomized trial (OASIS 3). Presented at the 2024 Annual Meeting of The Menopause Society. Chicago, Illinois. September 10-14, 2024.
2. Fitch J. Elinzanetant long-term safety data with JoAnn Pinkerton, MD, FACOG, NCMP. Contemporary OB/GYN. September 12, 2024. Accessed September 13, 2024. https://www.contemporaryobgyn.net/view/elinzanetant-long-term-safety-data-with-joann-pinkerton-md-facog-ncmp