Neuroprotection and Inflammation Reduction, Improvement in Biomarkers From ACT-AD Study: Hans J. Moebius, MD, PhD


At the 2023 AAN Annual Meeting, the chief medical officer at Athira Pharma spoke about findings from a phase 2 trial in which various biomarkers related to neurodegeneration showed significant improvements. [WATCH TIME: 4 minutes]

WATCH TIME: 4 minutes

“In a nutshell on that level, the biomarker level and also clinical outcomes, all flags point in the right direction. This is why we're confident we will, with an amended LIFT-AD trial [and ACT-AD trial], provide primary evidence of safety and efficacy [with fosgonimeton].”

Research has primarily targeted proteotoxicity and despite the multifactorial nature of AD, there is a need for approaches addressing other contributory factors. Fosgonimeton, a small-molecule positive modulator of the hepatocyte growth factor (HGF)/MET system, was evaluated in the randomized, double-blind, placebo-controlled, phase 2 ACT-AD study (NCT04491006). The trial assessed changes from baseline in plasma biomarkers in patients with mild-to-moderate Alzheimer’s disease (AD) treated with the agent.1

At baseline, blood samples were collected from 77 patients and then again at week 26 of treatment. Biomarkers such as neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), YKL-40, and amyloid beta 40 and 42 (Aβ40, Aβ42) were assessed. In fosgonimeton-treated subjects, results showed a statistically significant change from baseline compared with placebo in NfL (−7.9 pg/mL; SE, 2.7; P = .0059) and favorable directionally improvements in GFAP (−29.3 pg/mL; SE, 28.6; P = .312), YKL-40 (−34.9 ng/mL; SE, 26.5; P = .195), and Aβ42/40 ratio (0.0066; SE, 0.0035; P = .064).

Hans J. Moebius, MD, PhD, presented these findings in an oral presentation during the “Experimental Therapeutics in Dementia” session at the 2023 American Academy of Neurology (AAN) Annual Meeting, April 22-27, in Boston, Massachusetts.2 At the meeting, Moebius sat down with NeurologyLive® in an interview to provide an overview of the phase 2 trail. He talked about the observed changes and explained how the reduction in NFL levels after 6 months indicated neuroprotection. In addition, Moebius discussed the other biomarkers that were analyzed, and the significant improvements they showed compared with the placebo.

Click here for more coverage on AAN 2023.

1. Moebius H, Ooi KB, Hale M, et al. Fosgonimeton Provides Congruent Improvements on Neurodegeneration Biomarkers, Significantly Correlating With Composite Clinical Score of Cognition and Function in Alzheimer’s Disease. Presented at: 2023 AAN Annual Meeting; April 22-27; Boston, MA. Abstract 4214. Experimental Therapeutics in Dementia session.
2. Athira Pharma Presents New Clinical and Preclinical Data at the American Academy of Neurology (AAN) 2023 Annual Meeting. News Release. Athira Pharma. Published April 25, 2023. Accessed Mar 12, 2023.
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