Could One Injection a Month Suppress Menopausal Hot Flashes? ABCL635 Phase 2 Trial Shows Positive Signals

Menopausal hot flashes may seem brief, but repeated episodes can disrupt sleep, work, and daily life. AbCellera announced that the experimental antibody ABCL635 significantly reduced the frequency and severity of moderate-to-severe vasomotor symptoms in a Phase 2 trial and showed favorable preliminary tolerability. The result points to another potential nonhormonal treatment approach: instead of taking medication every day, patients could receive a long-acting subcutaneous injection that blocks the neural signals triggering symptoms.

ABCL635 targets the neurokinin 3 receptor (NK3R). The decline in estrogen after menopause disrupts the balance of KNDy neurons in the hypothalamus that are involved in temperature regulation. Neurokinin B continues to activate these neurons through NK3R, potentially causing the body to overactivate heat-dissipation responses and leading to sudden sensations of heat, sweating, and night sweats. By binding to NK3R and blocking this signaling pathway, ABCL635 is intended to narrow the dysregulated thermoregulatory range again.

Trial registration NCT07118891 covers Phases 1 and 2 and is expected to enroll 136 participants in total. Phase 2 Part C involves postmenopausal women with moderate-to-severe symptoms and randomly compares a single subcutaneous injection of ABCL635 with placebo; the registry lists participants, care providers, and investigators as blinded. A design previously disclosed by the company indicated that the Phase 2 proof-of-concept portion included approximately 80 participants, tested a single 600-milligram dose, and primarily assessed changes in symptoms and tolerability over the four weeks after treatment.

In its August 10 topline announcement, AbCellera said the treatment group outperformed placebo in both symptom frequency and severity, while overall tolerability was also consistent with expectations. However, ClinicalTrials.gov had not posted study results as of its June 15 update. Full statistical analyses suitable for independent review, baseline characteristics for each group, details of all adverse events, and longer-term follow-up are also currently lacking. It is therefore not yet possible to determine how long the effect can be maintained or whether rare risks might emerge in larger studies.

The long half-life of antibodies is the main distinction of this strategy. AbCellera hopes to develop the treatment as a once-monthly subcutaneous injection that patients can self-administer and maintains that its design may not require routine liver enzyme monitoring. However, this remains the target profile for the candidate product, not prescribing information confirmed by a regulatory authority. Phase 2 results from a single administration are also insufficient to establish the convenience, safety, and adherence associated with repeated long-term injections.

ABCL635 remains an investigational drug and must undergo larger and longer late-stage trials before it can reach clinical use. Its value will ultimately depend not only on whether it can rapidly reduce hot flashes, but also on whether its effects persist across the entire dosing interval, can be reproduced in different patient populations, and are supported by complete data demonstrating the benefit-risk profile of long-term use.