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Molecular Comparison and Safety Profiles of Fezolinetant and Elinzanetant
Panelists discuss why elinzanetant is likely to be associated with a lower risk of liver injury due to its distinct molecular structure compared to fezolinetant, and compare the adverse event profiles of the 2 drugs, highlighting that elinzanetant is more commonly associated with headache and fatigue while fezolinetant is linked to abdominal pain, diarrhea, insomnia, and back pain.
Episode 5
The following transcript has been edited for clarity, style, and length
Mary Jane Minkin, MD: Absolutely. From my understanding of the elinzanetant trials, there haven’t been significant liver function test abnormalities or notable treatment-emergent adverse events. Lisa, perhaps you can weigh in, but it seems the liver activity issues we’ve seen with fezolinetant aren’t related to receptor activity. Instead, they seem to stem from the molecule itself.
Elinzanetant and fezolinetant are distinct molecules, though they may share some binding mechanisms.
Lisa Larkin, MD: Exactly. As with most things in medicine, it’s rarely a simple cause-and-effect relationship—it’s multifactorial. We don’t yet fully understand why fezolinetant has been associated with liver function test abnormalities.
Elinzanetant, being a different molecule, hasn’t shown the same liver concerns in trials so far. However, because it’s in the same drug class, it’s possible the FDA might recommend similar monitoring protocols if and when it’s approved. We’ll have to wait and see. What we do know is that these molecules are different, and the studies to date suggest distinct effects and side effect profiles.
Minkin: Not all receptor binders are created equal, which could explain the differences in activity and outcomes between the drugs. On the topic of adverse events, it’s worth noting that most medications have minor side effects that bother some patients, and we see similar complaints in placebo groups. With elinzanetant, treatment-emergent adverse events seem relatively mild, with fatigue and headaches being the most common complaints.
Larkin: Right. And for fezolinetant , the side effect profile appears different, with some gastrointestinal issues noted. Even in clinical trials, the emergent side effects vary between these drugs, reflecting their molecular differences.
