Nonhormonal elinzanetant effective long-term for reducing hot flash frequency: OASIS 3

Key takeaways:

• Postmenopausal women taking elinzanetant reported fewer daily moderate to severe hot flashes for up to 50 weeks vs. placebo.
• The study reflected a real-world population with less severe vasomotor symptoms.

CHICAGO — Nonhormonal elinzanetant was associated with fewer moderate to severe vasomotor symptoms compared with placebo for up to 1 year, along with similar long-term positive safety data, researchers reported.

Healio previously reported topline results of the phase 3 OASIS 3 study in March.

“The women in this trial are much more similar to your average patient who comes into the office with hot flashes, night sweats and sleep disturbance,” James A. Simon, MD, CCD, MSCP, IF, FACOG, medical director and founder of IntimMedicine Specialists and clinical professor at George Washington University, told Healio. “These data are likely to be more representative of the average patient and demonstrated efficacy in that setting. The primary reason for this study was to assess longer-term safety of elinzanetant in the population most likely to use it, and it showed really good safety over the course of about a year.”

For the OASIS 3 study, researchers analyzed data from 628 postmenopausal women aged 40 to 65 years with moderate to severe vasomotor symptoms (mean age, 55 years). Researchers randomly assigned women oral elinzanetant (Bayer) 120 mg (n = 313) or placebo (n = 315) once daily for 52 weeks.

James A. Simon

The primary outcome was mean change in moderate to severe vasomotor symptom frequency from baseline to 12 weeks, assessed by hot flash daily diary. Secondary outcomes included mean change in Patient-Reported Outcomes Measurement Information System Sleep Disturbances Short Form (PROMIS SD SF) 8b total T-score and Menopause-Specific Quality of Life (MENQoL) total score from baseline to 12 weeks.

At 12 weeks, the elinzanetant group experienced a mean of 1.6 daily moderate to severe vasomotor symptoms compared with 3.4 in the placebo group (least-squares mean difference, –1.6; 95% CI, –2 to –1.1; P < .0001). Reductions were maintained through week 50

In addition, the elinzanetant group experienced a mean change of –9.4 for the PROMIS SD SF 8b total T-score and –1.3 for the MENQoL score while the placebo group experienced smaller changes of –5.7 and –1.1, respectively, from baseline to 52 weeks.

Regarding safety, 30.4% of women in the elinzanetant group and 14.6% in the placebo group experienced treatment-emergent adverse events, including headache, fatigue and excessive sleepiness. There were no unexpected changes in bone mineral density changes or body weight from baseline to 52 weeks.

Researchers observed no cases of endometrial hyperplasia or malignant neoplasm in either treatment group. According to Simon, there were also no liver safety signals and no hepatoxicity.

“Elinzantant should be efficacious for individuals, even those not as severely affected as women in OASIS 1 and 2, with a good safety profile, both in terms of side effects and any adverse events common to estrogens or the class of drugs that modulate the neurokinin system. That has been an ongoing issue for other agents in this class ... but was not seen in OASIS 3 or with elinzanetant, and that’s very positive,” Simon told Healio. “Sleep and menopause-specific quality of life benefits were demonstrated in these studies, and the benefits were maintained for the entire study, as opposed to just an efficacy study. At 12 weeks, these benefits for hot flashes, night sweats, sleep and quality of lifewere all maintained throughout the course of this longer-term study.”

For more information:

James A. Simon, MD, CCD, MSCP, IF, FACOG, can be reached at jsimon@intimmedicine.com.