Athira Pharma’s experimental Alzheimer’s therapy, fosgonimeton, continues to show signs of being able to improve cognition and function in patients.
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Athira Pharma’s experimental Alzheimer’s therapy, fosgonimeton, continues to show reductions in known biomarkers associated with the disease and signs of cognitive and functional improvement in patients with mild-to-moderate Alzheimer’s.
On Thursday, Bothell, Wash.-based Athira presented biomarker data from the Phase II ACT-AD study showing that fosgonimeton produced reductions in biomarkers of neurodegeneration (NfL) and neuroinflammation (GFAP) compared to placebo among patients who were not taking acetylcholinesterase inhibitors.
The data, presented at the 15th Clinical Trials on Alzheimer’s Disease (CTAD) conference, will further inform the necessary sample size required for Athira’s ongoing Phase II/III LIFT-AD study.
Fosgonimeton is a small molecule designed to enhance the activity of hepatocyte growth factor and its receptor, MET, in order to impact neurodegeneration and regenerate brain tissue.
Hans J. Moebius, chief medical officer at Athira, told BioSpace the biomarker improvements also significantly correlated with improvements in clinical outcomes at week 26.
Earlier this year, Athira reported the ACT-AD study missed meeting its primary endpoint. However, a planned analysis of subgroup data showed cognitive and functional improvements through fosgonimeton’s modulation of the HGF/MET system. This allowed Athira to amend its LIFT-AD study to investigate the drug as a monotherapy.
The data suggested there was a drug interaction that reduced the benefits between fosgonimeton and the concomitant acetylcholinesterase inhibitors in the control group, Moebius said.
He added that there was a sizeable difference in efficacy between patients who received the combination compared to fosgonimeton alone, and improvements in biomarker data were larger and statistically significant in fosgonimeton-only patients.
“The bottom line is we can conclude that clinical endpoints are highly correlated to biomarkers of neurodegeneration and neuroinflammation,” Moebius said. “It’s neuroprotective and [it] is improving blood-based biomarkers and the clinical outcomes.”
He noted the company will enroll up to 150 additional patients to ensure the LIFT-AD trial is well-powered to achieve its primary endpoint. Full enrollment of the Phase II/III trial is expected in the middle of 2023, with topline results coming in early 2024.
An Increasingly Competitive Space
Athira’s results were announced two days after Eisai presented data from the Phase III CLARITY AD trial of lecanemab, which showed a slowing of cognitive decline in some patients.
Howard Fillit, cofounder and chief scientific officer of the Alzheimer’s Disease Defense Foundation, said the data is “welcome news” for Alzheimer’s patients. However, he said it should only be a starting point to defeating the disease.
“We have a lot of ground to cover to get from the 27% slowing lecanemab offers to our goal of slowing cognitive decline by 100%.”
Moebius speculated that the Eisai data would ultimately result in regulatory approval of lecanemab. Still, like Fillit, he said more work needs to be conducted to bring greater benefit to Alzheimer’s patients.
Looking at the significant need in the Alzheimer’s community, Moebius said he believes the FDA has maintained unwavering support for new therapeutics for this indication, something he believes will still be in effect when Athira is ready to take fosgonimeton to the regulator.
