The respite for Athira Pharma was short-lived. Having won its proxy fight last month, the biotech has now walked right into a phase 2 failure in Alzheimer’s disease, leaving it clinging to a prespecified subgroup analysis for evidence that fosgonimeton has a future in the indication.
Over the past year, Athira’s work has been overshadowed by an investigation into whether its then-CEO altered images, which led to her ousting, and a subsequent push by an activist investor to shake up the C-suite and board of directors. The phase 2 readout offered Athira a chance to recenter the narrative on the promise of its clinical pipeline. Instead, the data drop has raised questions about its prospects.
The clinical trial randomized 77 patients with mild to moderate Alzheimer’s to receive one of two doses of the hepatocyte growth factor receptor agonist fosgonimeton or placebo for 26 weeks. At the end of the treatment period, fosgonimeton failed to beat placebo in terms of the change in ERP P300 latency, a measure of working memory processing speed.
That failure caused the trial to miss its primary endpoint. A clutch of secondary endpoints looked at the effect of fosgonimeton on measures of cognition, global clinical change and functional change. Again, the drug candidate failed to beat placebo.
Despite the clean sweep of failures, Hans Moebius, M.D., Ph.D., chief medical officer at Athira, hailed aspects of the results as “very encouraging” in a statement disclosing the data. Moebius’ upbeat assessment is based on a prespecified subgroup analysis that indicated “a potential diminished effect” of fosgonimeton when given in combination with standard-of-care acetylcholinesterase inhibitors (AChEIs). Sixty percent of the participants remained on stable doses of AChEIs while in the study.
In a post hoc analysis, Athira zeroed in on the 40% of participants who received fosgonimeton as a single agent. Athira saw a “potentially beneficial” 28-millisecond change in ERP P300 latency in the analysis, as well as -3.3-point change on the ADAS-Cog11 measure of cognitive improvement. The signs of efficacy were enough for Athira to attempt to put a positive spin on the results.
“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,” Moebius said. “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.”
Exactly what the “rational optimization” of the phase 3 LIFT-AD trial, which has an estimated completion date in the fall, will entail is unclear. Athira plans to talk to its advisers, investigators and regulators about how to adapt the study. The LIFT-AD inclusion criteria permit stable AChEI treatment.