Athira Pharma Reports Phase 2/3 LIFT-AD Trial Results for Fosgonimeton in Mild-to-Moderate Alzheimer's

Athira Pharma, Inc., a biopharmaceutical company in the late stages of clinical development, recently disclosed results from its Phase 2/3 LIFT-AD trial for fosgonimeton, aimed at treating mild-to-moderate Alzheimer's disease (AD). Fosgonimeton is a hepatocyte growth factor (HGF) positive modulator intended to enhance neuronal health and slow down neurodegeneration.

The primary aim of the LIFT-AD trial was to assess changes from baseline in a combined measure of cognition and function using the Global Statistical Test (GST), which includes ADAS-Cog11 for cognition and ADCS-ADL23 for daily function. Unfortunately, the trial did not meet its primary endpoint or key secondary endpoints, as neither the GST nor its components reached statistical significance at the 26-week mark compared to the placebo. Despite this, both measures of cognition and function showed a trend favoring fosgonimeton.

Interestingly, in pre-specified subgroups of patients with moderate Alzheimer's or who were APOE4 carriers, treatment effects of fosgonimeton were more pronounced. These subgroups displayed either improvement or stabilization in cognitive and functional measures. Furthermore, fosgonimeton treatment led to favorable changes across biomarkers linked to Alzheimer's pathology, including protein pathology markers (Aβ42/40, p-Tau181, and p-Tau217), inflammation (GFAP), and neurodegeneration (NfL).

Dr. Javier San Martin, Chief Medical Officer at Athira, acknowledged that the results were not as expected, attributing the lack of significant clinical decline in the placebo group and the short duration of the study as potential factors. Dr. Anton P. Porsteinsson from the University of Rochester, a LIFT-AD investigator, emphasized the consistency and intriguing nature of the biomarker and subgroup data, which align with the known neuroprotective mechanism of fosgonimeton's HGF modulation.

The LIFT-AD trial was a double-blind, placebo-controlled study involving 312 patients with mild-to-moderate Alzheimer's disease, who were not on acetylcholinesterase inhibitors. Participants received daily subcutaneous fosgonimeton injections (40 mg) for 26 weeks. Biomarker analyses post-treatment consistently indicated improvements in neurodegeneration markers, inflammation, and protein pathology, favoring fosgonimeton over placebo.

The safety profile of fosgonimeton was generally positive, with a higher incidence of treatment-emergent adverse events compared to the placebo, primarily due to injection site reactions. However, the incidence of serious adverse events was comparable between the two groups, and no deaths were reported.

Dr. Mark Litton, President and CEO of Athira, extended gratitude to the patients, caregivers, and healthcare professionals involved in the LIFT-AD trial. He also noted that Athira is advancing its research pipeline, including next-generation, orally delivered HGF modulators like ATH-1105 for diseases such as amyotrophic lateral sclerosis (ALS) and Alzheimer's. ATH-1105 is currently undergoing a Phase 1 clinical trial to assess safety, tolerability, and pharmacokinetics in healthy volunteers, with plans to move into ALS patient trials by 2025.

Athira plans to present a full analysis of the LIFT-AD trial results at the 17th Annual Clinical Trials on Alzheimer’s Disease (CTAD) conference in Madrid, Spain, from October 29 to November 1, 2024. The company continues its commitment to developing treatments that could potentially alter the trajectory of neurodegenerative diseases.

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