Athira Pharma, Inc. a late clinical-stage biopharmaceutical company focused on developing small molecules to restore neuronal health and slow neurodegeneration, today announced topline results from its exploratory ACT-AD Phase 2 study of fosgonimeton in patients with mild-to-moderate Alzheimer’s disease. Fosgonimeton is a small molecule designed to enhance the activity of Hepatocyte Growth Factor and its receptor, MET, which are expressed in the central nervous system to promote brain health and function.
“Following compelling ERP P300 latency biomarker data from a small Phase 1b trial over eight days in Alzheimer’s patients on fosgonimeton monotherapy, this Phase 2 trial provides valuable insights into the nature of this novel intervention over 26 weeks. ACT-AD was designed as a learning study to further investigate the ERP P300 biomarker signal over 6 months, assess safety in a patient population more representative of the real world, by allowing the use of add-on standard-of-care acetylcholinesterase inhibitors (AChEIs, e.g., donepezil), and explore fosgonimeton’s effect on psychometric outcomes, including ADAS-Cog11, to inform the ongoing Phase 3 LIFT-AD study. To that end, this study achieved its goal,” said Hans Moebius, M.D., Ph.D., Chief Medical Officer of Athira.
“The study was intended to show differences on the biomarker ERP P300 latency. This primary endpoint was not met by protocoled analysis, however a pre-specified subgroup analysis indicated a potential diminished effect of fosgonimeton when given in combination with AChEIs. A subsequent post hoc analysis of the data from patients on fosgonimeton monotherapy showed a meaningful improvement in both ERP P300 latency and cognitive performance compared to placebo at 26 weeks.
“These data points are very encouraging as they indicate the expected pharmacological activity of fosgonimeton by parallel improvement on ERP P300 latency and ADAS-Cog11 and show a favorable safety profile over six months. This is the first time monotherapy fosgonimeton has shown an effect on ADAS-Cog11, suggesting a potential cognitive benefit. We will use these insights for a rational optimization of the ongoing LIFT-AD trial. We plan to seek advice from our scientific advisors, investigators, and ultimately regulators on how to expeditiously analyze and potentially adapt the LIFT-AD study,”
Dr. Moebius
“The data from the fosgonimeton monotherapy analysis are encouraging and show biologic activity that may support the potential role of the HGF/MET pathway in neurodegenerative diseases,” said Marwan Sabbagh, M.D., FAAN, professor of neurology at Barrow Neurological Institute, Phoenix, AZ. “ACT-AD adds to the body of literature suggesting ERP P300 latency as an important biomarker for cognitive status.”