The investigational injection fosgonimeton appeared to have better efficacy in patients with more severe disease, according to post-hoc subgroup analyses, though none resulted in statistically significant effects.
Athira Pharma announced on Tuesday that its investigational injection fosgonimeton failed the Phase II/III LIFT-AD trial, unable to significantly boost cognition or function in patients with mild-to-moderate Alzheimer’s disease.
Topline data from LIFT-AD showed that fosgonimeton improved scores on the Global Statistical Test—which combines results from cognition and function measures—by 0.08 points. However, this effect fell short of statistical significance, with a p-value of 0.7, according to Athira. Fosgonimeton also had slightly beneficial effects on cognition and function when measured individually, but the magnitude of its effect on either metric also did not reach statistical significance.
“These are not the results we hoped for,” Athira Chief Medical Officer Javier San Martin said in a statement, noting that the “lack of clinical decline in the placebo group” and the overall short study duration “may have impacted the trial’s ability to translate the effect of fosgonimeton treatment into meaningful clinical benefit.”
Still, San Martin said that “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.”
LIFT-AD also assessed the effects of fosgonimeton on biomarkers and found significant improvements in various indicators of neurodegeneration, inflammation and protein pathology. A subgroup analysis showed that fosgonimeton resulted in a “greater numerical treatment effect” in patients with more advanced disease.
Post-hoc subgroup analyses likewise revealed better outcomes for patients with worse disease severity or those who had clinical dementia at baseline, and this beneficial effect was driven by cognitive improvements. However, none of these sub-analyses found statistically significant effects for fosgonimeton.
Still, Anton Porsteinsson, director of the Alzheimer’s Disease Care, Research and Education Program at the University of Rochester, said in a statement that these biomarker and subgroup findings are “remarkably consistent not only across endpoints but also with our understanding of fosgonimeton’s neuroprotective mechanism of action.” Porsteinsson is an investigator for LIFT-AD.
Designed to be administered via a simple subcutaneous injection, fosgonimeton is an investigational small molecule drug that works by boosting the activity of the neurotrophic hepatocyte growth factor system, which could potentially protect or promote the repair of neuronal networks. Through this mechanism of action, fosgonimeton has therapeutic potential for several neurodegenerative disease.
In addition to Alzheimer’s disease, Athira is developing fosgonimeton for Parkinson’s disease dementia and dementia with Lewy bodies. The biotech released exploratory Phase II data for these in December 2023, noting that the drug candidate had overall positive effects on cognition.
