Athira's Alzheimer’s Drug Trial Yields Mixed Results

Athira Pharma, Inc. (NASDAQ: ATHA), a biopharmaceutical firm in late-stage development that targets neuronal health and neurodegeneration with small molecules, has revealed the preliminary outcomes from its Phase 2/3 LIFT-AD study. This trial evaluated fosgonimeton, a positive modulator of hepatocyte growth factor (HGF), in individuals with mild-to-moderate Alzheimer's disease (AD).

The topline results indicated that the primary endpoint of the trial, the Global Statistical Test (GST) — which combines measures of cognition (ADAS-Cog11) and function (ADCS-ADL23) — as well as the key secondary endpoints of ADAS-Cog11 and ADCS-ADL23, did not achieve statistical significance compared to the placebo at 26 weeks. However, both GST components showed a directional benefit for fosgonimeton treatment. 

In pre-defined subgroups with faster disease progression (such as moderate AD and APOE4 carriers), improvements or stabilization in cognition and function were observed in the fosgonimeton group. Additionally, biomarkers related to protein pathology (Aβ42/40, p-Tau181, and p-Tau217), inflammation (GFAP), and neurodegeneration (NfL) exhibited directional improvements with fosgonimeton treatment, aligning with its proposed neuroprotective effects through HGF modulation.

Javier San Martin, M.D., Chief Medical Officer of Athira, said in a statement, “These are not the results we hoped for, as the lack of clinical decline in the placebo group, combined with the short duration of the study, may have impacted the trial’s ability to translate the effect of fosgonimeton treatment into meaningful clinical benefit. However, we believe the totality of the data continues to suggest that positive modulation of the HGF pathway has the potential to translate into improvement in parameters of neuronal health and may mitigate disease progression.”

“While the trial did not meet its primary endpoint, the biomarker and subgroup data are intriguing and remarkably consistent not only across endpoints but also with our understanding of fosgonimeton’s neuroprotective mechanism of action,” FDA Supports Innocan Pharma’s Liposomal CBD; Anton P. Porsteinsson, M.D., Comments.