Clinical Report: Hepatic Safety of Elinzanetant for Menopausal and Breast Cancer VMS
Overview
Elinzanetant 120 mg demonstrates a low risk of liver injury in women treated for vasomotor symptoms related to menopause or endocrine therapy for breast cancer. Clinical trials and an independent liver safety board found no serious liver adverse events, with mild liver enzyme changes comparable to placebo.
Background
Vasomotor symptoms (VMS), such as hot flashes, affect up to 80% of postmenopausal women and are also common and severe in women undergoing endocrine therapy for breast cancer. The KNDy neurons in the hypothalamus, which express NK-1 and NK-3 receptors, are implicated in VMS pathophysiology. Elinzanetant, a dual NK-1/-3 receptor antagonist, is a nonhormonal treatment option shown to be effective for moderate-to-severe VMS. Given concerns about drug-induced liver injury (DILI) with other NK-3 antagonists, hepatic safety was closely monitored during elinzanetant’s clinical development.
Data Highlights
Study Phase
Participants (Elinzanetant)
Participants (Placebo)
Duration
Findings
Phase 1
537
245
Single and repeated doses
No clinically relevant liver enzyme elevations or hepatotoxicity
Phase 2 (RELENT-1, SWITCH-1, NIRVANA)
Postmenopausal women with VMS
Placebo-controlled
Varied
Low incidence of mild liver enzyme changes, comparable to placebo
Phase 3 (OASIS 1, 2, 4)
Women with menopausal or endocrine therapy-related VMS
Placebo-controlled
12 to 52 weeks, extension ongoing
No serious liver adverse events; mild changes similar to placebo; no liver monitoring required post-approval
Key Findings
Elinzanetant lacks structural features associated with hepatotoxicity and is metabolized primarily by CYP3A4 without formation of reactive intermediates.
Preclinical toxicology studies up to 2 years showed no liver safety concerns.
Clinical trials involving over 500 elinzanetant-treated participants showed no serious liver injury and mild liver enzyme changes comparable to placebo.
An independent liver safety board concluded that routine liver test monitoring is unnecessary after regulatory approval.
Unlike fezolinetant, another NK-3 antagonist with rare serious liver injury risk, elinzanetant’s dual NK-1/-3 antagonism and metabolic profile suggest a safer hepatic profile.
Clinical Implications
Clinicians can consider elinzanetant 120 mg a safe nonhormonal option for managing moderate-to-severe VMS in postmenopausal women and those undergoing endocrine therapy for breast cancer without the need for routine liver enzyme monitoring. This safety profile supports its use in populations at risk for liver injury, improving treatment adherence and patient outcomes.
Conclusion
Elinzanetant demonstrates a favorable hepatic safety profile with low risk of liver injury, supporting its clinical use for vasomotor symptoms related to menopause and endocrine therapy. Ongoing long-term data continue to affirm its liver safety.
References
OASIS Studies and Clinical Trials Data -- Elinzanetant Hepatic Safety
FDA and EMA Warnings on Fezolinetant -- Liver Injury Risk
LiverTox Database -- NK-1 and NK-3 Antagonists Hepatic Profiles
