ESOC 2025 | A sub-analysis of ESCAPE-NEXT: neurofilament light chain as a marker of neuroaxonal injury

ESCAPE-NEXT was a Phase III global clinical trial that investigated the efficacy and safety of nerinetide. Nerinetide is a PSD95 inhibitor and there was preclinical and also earlier Phase III evidence that narenotide could improve outcomes in a particular group of patients. Those that undergo thrombectomy but they do not receive thrombolysis. ESCAPE-NEXT yielded neutral clinical results but we conducted the biomarker sub-study with the aim of investigating whether neurofilament light chain would serve as a surrogate marker for predicting clinical treatment effects. Neurofilament light is a protein that is located in the axons of all our neurons and if these neurons die during ischemic stroke they’re released to the bloodstream and then you can find them in a blood sample and you can see how they rise after stroke. The hypothesis was that the higher the levels of neurofilament, the more brain injury we have, particularly or potentially better to define this compared to imaging. And indeed we found in a subset of the ESCAPE-NEXT trial population in 200 patients, so approximately 20% of the population, we found that there’s an effect of the medication of nerinetide on neurofilament levels, saying that this population might benefit in terms of the outcome of a neuroaxonal injury marker while the clinical effect has yet to be seen.

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