Clinical Trials · north_america
Hot Flashes Reduced by 80% After a Single Injection: Long-Acting NK3R Antibody Passes Phase 2 Proof of Concept
AbCellera announced preliminary results from a 92-person randomized trial showing that ABCL635 substantially reduced moderate to severe menopausal hot flashes within four weeks, with no serious adverse events observed; however, the full data have not yet been disclosed, and how long the efficacy can be maintained remains to be confirmed.
Menopausal hot flashes are often more than just a brief sensation of heat; they can repeatedly disrupt sleep, work, and daily life. AbCellera’s long-acting antibody ABCL635 has now shown in a Phase 2 trial that, after just one subcutaneous injection, participants experienced an average 83% reduction in the frequency of moderate to severe hot flashes after four weeks, compared with a 33% reduction in the placebo group. This difference opens another development pathway for nonhormonal treatments that may offer a longer duration of action.
This randomized, double-blind, placebo-controlled proof-of-concept study enrolled 92 postmenopausal women with moderate to severe vasomotor symptoms. According to the topline results announced by the company, the trial met its prespecified primary endpoint; in addition to the number of episodes, symptom severity also improved significantly. However, AbCellera has not disclosed the number of participants in each group, the dose, statistical estimates, or the specific changes in severity, so it is not yet possible to fully assess the magnitude of the effect or the differences among participants.
ABCL635 targets the neurokinin 3 receptor (NK3R). This receptor is part of the signaling pathway of KNDy neurons in the hypothalamus that regulate body temperature; the decline in estrogen after menopause disrupts this regulatory mechanism, triggering hot flashes. Existing NK3R-related therapies are primarily small-molecule drugs, while ABCL635 seeks to use the antibody’s longer residence time in the body to enable once-monthly treatment rather than daily medication.
Earlier Phase 1 data provided preliminary support for this dosing concept: single doses ranging from 30 to 900 mg had an estimated half-life of approximately 24 days, and inhibition of a biomarker associated with NK3R activity persisted for four weeks in a dose-dependent manner. These pharmacodynamic signals show that the antibody did engage the intended pathway, but biomarker changes cannot substitute for clinical efficacy; the symptom improvement in this Phase 2 trial provides the more direct proof of concept.
Regarding safety, the company said there were no serious adverse events in the trial and no participants discontinued treatment because of it; the earlier Phase 1 trial likewise found no serious adverse events or elevations in liver enzymes. However, the topline announcement did not provide the types, incidence, or severity of common adverse events, or differences between groups. For a menopausal treatment that may be used long term, tolerability after repeated dosing still needs to be addressed in larger and longer studies.
The study design listed on ClinicalTrials.gov shows that Phase 2 participants were followed for 12 weeks after a single dose and could then choose to enter an open-label extension period; registered endpoints also include quality of life and sleep disturbance. To date, no results have been posted on the trial registration page. Whether ABCL635 can sustain its four-week effect through the full follow-up period, improve sleep and quality of life, and reproduce its efficacy in subsequent trials will determine whether this antibody can progress from striking preliminary figures to a practical treatment option.