Athira Pharma presented results from its Phase 2/3 LIFT-AD clinical trial of fosgonimeton for treating Alzheimer’s disease (AD) at the 17th Annual Clinical Trials on Alzheimer’s Disease (CTAD) conference in Madrid, Spain, held from October 29 to November 1, 2024. While the trial did not achieve statistical significance for the primary endpoint, the Global Statistical Test (GST), certain subgroups showed promising results.
LIFT-AD Trial Outcomes
The LIFT-AD trial's topline results, previously reported, indicated that fosgonimeton did not meet the primary endpoint of GST or key secondary endpoints at 26 weeks when compared to placebo. However, both components of the GST, cognition (ADAS-Cog11) and function (ADCS-ADL23), showed directional favor towards fosgonimeton treatment.
Subgroup Analysis
Pre-specified subgroups, characterized by more rapid disease progression such as those with moderate AD and APOE4 carriers, demonstrated improved or stabilized cognition and function in the fosgonimeton-treated group. These findings suggest a potential benefit in specific patient populations.
Biomarker Data
Data from biomarkers of protein pathology (Aβ42/40, p-Tau181, and p-Tau217), inflammation (GFAP), and neurodegeneration (NfL) displayed directional changes favoring fosgonimeton treatment. These changes align with the neuroprotective mechanism of HGF modulation.
Future Directions with ATH-1105
Athira is now focusing on advancing ATH-1105, an oral, next-generation small molecule positive modulator of the neurotrophic hepatocyte growth factor (HGF) system. This compound is being explored as a potential treatment for neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS) and Alzheimer’s disease (AD).
ATH-1105 Phase 1 Trial
Currently, Athira is conducting a Phase 1 double-blind, placebo-controlled trial (NCT 06432647) with up to 80 healthy volunteers to assess the safety and tolerability of ATH-1105, including pharmacokinetic measurements. The first cohort was completed in June 2024, and the full study is expected to be completed by the end of 2024, with plans to begin dosing ALS patients in 2025.
Expert Commentary
"We believe the totality of the data supports the potential of HGF modulation for the treatment of neurodegenerative diseases," said Javier San Martin, M.D., Chief Medical Officer of Athira.
