Elinzanetant Effective for Menopause Symptoms Across BMI, Smoking Status

Elinzanetant significantly reduced vasomotor symptoms (VMS), also known as hot flashes, associated with menopause overall and across a range of body mass index (BMI) and smoking history subgroups, according to pooled data from the phase 3 OASIS-1 (NCT05042362) and OASIS-2 (NCT05099159) trials.1,2 The findings were presented at the 2025 Academy of Managed Care Pharmacy Annual Meeting.

Pooled data demonstrated elinzanetant's efficacy overall and across BMI and smoking status subgroups. | Image credit: Monkey Business - stock.adobe.com

Elinzanetant, a dual neurokinin-1 (NK-1) and NK-3 receptor antagonist, significantly reduced the frequency and severity of VMS compared with placebo overall in the OASIS-1 and OASIS-2 trials, according to one abstract presented at the meeting.1 Pooled data from the studies also showed improved sleep disturbances and menopause-related quality of life, as well as a favorable safety profile.

Across both studies, a total of 796 women experiencing at least 50 moderate to severe VMS events per week were randomized to receive either elinzanetant for 26 weeks (n = 399) or a placebo for 12 weeks followed by elinzanetant for 14 weeks (n=397). End points in the pooled analysis included VMS frequency from baseline to 1, 4, and 12 weeks; severity of VMS from baseline to 4 and 12 weeks; PROMIS sleep disturbance short form 8b total T-score (SDSF8B) at baseline and week 12; and menopause-specific quality of life questionnaire (MENQOL) total scores at baseline and week 12. A mixed model with repeated measures analyzed outcomes, and the P values were indicative, not confirmatory.

At weeks 4 and 12, mean (SD) VMS frequency reductions were 8.02 (7.65) and 9.35 (8.66), respectively, with elinzanetant vs 5.24 (7.95) and 6.41 (9.36) with placebo. The differences were nominally significant as early as week 1 (P < .0001), as well as at 4 and 12 weeks. Mean VMS severity reductions were also greater with elinzanetant (0.74 [0.66] at 4 weeks and 0.96 [0.78] at 12 weeks) compared with placebo (0.46 [0.50] at 4 weeks and 0.61 [0.64] at 12 weeks). Reductions were nominally significant at weeks 4 and 12.

Mean PROMIS sleep disturbance and MENQOL scores were also better with elinzanetant at week 12. SDSF8B reduced by 10.7 (8.7) with elinzanetant vs 5.3 (6.9) with placebo, while MENQOL scores reduced by 1.37 (1.29) with treatment vs 0.96 (1.14) with placebo.

Additional numerical improvements in VMS, SDSF8B, and MENQOL measures were seen in patients who switched from placebo to elinzanetant after week 12 through week 26.

"[Elinzanetant] is a well-tolerated, efficacious, novel non-hormonal treatment that significantly improves VMS frequency and severity in postmenopausal women with [moderate to severe] VMS,” the authors concluded. “Sleep disturbances and menopause-related quality of life were also improved.”

Another analysis aimed to determine elinzanetant’s effectiveness in prespecified BMI and smoking history subgroups using pooled data from the trials.2 These aspects could influence treatment choice, making them key to evaluate, the authors explained.

Participants in both the elinzanetant and placebo groups were evaluated by BMI, with 4 classifications, measured in kg/m2: BMI of less than 18.5 (n = 5 and n = 2, respectively), BMI of 18.5 to 25 (n = 124 and n = 118, respectively), BMI of 25 to 30 (n = 142 and n = 143, respectively), and BMI of 30 or higher (n = 128 and n = 134, respectively). They were also classified into 3 smoking history groups: never (n = 267 and n = 250, respectively), former (n = 67 and n = 66, respectively), and current (n = 65 and n = 81, respectively).

Overall, elinzanetant consistently reduced daily hot flash frequency across BMI categories and smoking statuses at 12 weeks. Women with a BMI of 30 or higher experienced a mean (SD) VMS reduction of 9.7 (11.5) episodes per day with elinzanetant vs a reduction of 5.2 (11.5) with placebo. Those with a BMI of 18.5 to 25 experienced reductions of 8.8 (7.1) VMS episodes per day with elinzanetant vs 6.5 (6.3) with placebo, and the group with a BMI of 25 to 30 experienced reductions of 9.5 (6.8) vs 7.4 (9.2), respectively.

In the smoking status subgroups, the most significant benefit was seen among current smokers, who experienced a reduction of 11.2 (12.2) VMS episodes with elinzanetant vs a reduction of 7.4 (9.2) with placebo. VMS episodes were reduced by 7.8 (6.4) vs 5.4 (6.2) per day among former smokers treated with elinzanetant and placebo, respectively, and never smokers experienced reductions of 9.3 (8.1) vs 6.4 (10.1), respectively.

“[Elinzanetant] demonstrated greater numerical reductions than [placebo] in moderate-to-severe VMS frequency in postmenopausal women across all BMI and smoking history subgroups,” the authors concluded.

References

1. Simon J, Pinkerton J, Maki P, et al. Efficacy of elinzanetant for the treatment of vasomotor symptoms associated with menopause: pooled data from two phase 3 studies. Presented at: AMCP 2025; March 31-April 3, 2025; Houston, TX. Poster U25.
2. Simon J, Pinkerton J, Joff H, et al. Effect of elinzanetant for the treatment of vasomotor symptoms associated with menopause across BMI and smoking history subgroups: pooled data from two phase 3 studies. Presented at: AMCP 2025; March 31-April 3, 2025; Houston, TX. Poster U24.