The treatment is being developed as a first-in-class regenerative therapy for those with AD and dementia, with these safety data offering support to its development.
Recently published findings from a phase 1 clinical trial (NCT03298672) of fosgonimeton (Athira Pharma) show that the treatment was safe and well tolerated in patients with Alzheimer disease (AD). These results add support to the development of the treatment, previously known as ATH-1017, as a novel therapeutic for people with AD and dementia.1,2
Investigators included a total of 88 patients, including 48 healthy young men in a single ascending dose cohort, 29 healthy elderly volunteers in a multiple ascending dose cohort, and 11 patients with AD in a fixed-dose cohort. Across all doses, fosgonimeton was safe and well-tolerated, and pharmacokinetic results were dose-proportional, with no sex effect or accumulation over 9 days.
Investigators, led by Xue Hua, PhD, MS, vice president of clinical development, research, Athira Pharma, noted that the main treatment effect on qualitative electroencephalogram (qEEG) was acute and sustained γ power induction. Compared with placebo, in patients with AD, fosgonimeton demonstrated a statistically significant effect toward Event-Related Potential (ERP) P300 latency normalization (40-mg fosgonimeton: n = 7; placebo: n = 4; P = .027).
"These encouraging results showed a positive safety and tolerability profile of fosgonimeton across a wide dose range, and the pharmacodynamics support blood-brain barrier penetration. Importantly, we believe the significant reduction of ERP P300 latency levels seen in the Alzheimer’s disease patient cohort on active treatment may be suggestive of enhanced synaptic function and, ultimately, the potential procognitive properties of fosgonimeton,” Hans Moebius, MD, PhD, chief medical officer, Athira, said in a statement.1 “These data support our ongoing phase 2 ACT-AD and phase 3 LIFT-AD trials evaluating fosgonimeton's potential as a treatment for Alzheimer’s disease. We look forward to sharing the phase 2 ACT-AD top-line data in the second quarter of 2022.”
Both fosgonimeton and placebo were administered via daily subcutaneous injection. Those in the healthy single ascending dose cohort received doses between 2 mg and 90 mg, those in the multiple ascending dose cohort received doses between 20 mg and 80 mg, and those with AD received daily doses of 40 mg. Following treatment with fosgonimeton, qEEG and ERP P300 measured neurophysiological signals, supporting brain penetration and target engagement, according to Hua et al.
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In addition to the phase 1 study, fosgonimeton is also being evaluated in the phase 2 ACT-AD study (NCT04491006) in mild-to-moderate AD, which completed enrollment in Oct 2021; the phase 3 LIFT-AD study (NCT04488419) in mild-to-moderate AD, which is currently recruiting patients; an open label extension trial (NCT04886063) in mild-to-moderate AD, which is currently enrolling patients; and the phase 2 SHAPE trial (NCT04831281) in patients with Parkinson disease dementia or dementia with Lewy bodies, which is also currently recruiting.
Fosgonimeton, which is designed to enhance hepatocyte growth factor (HGF) to promote brain health and function, has shown positive results in preclinical trials to date. In an animal model of APP1/PS1 transgenic mice, treatment with ATH-1017 resulted in increased qEEG γ power that is associated with cognitive processing and memory.
The investigational agent also demonstrated safety, including no serious adverse events, in a phase 1a/1b clinical trial of healthy young, healthy elderly, and patients with AD. Additionally, it also showed a statistically significant improvement in ERP, and investigators noted ERP 300 latency among patients after multiple treatments with ATH-1017 compared with placebo (P <.05).3
Fosgonimeton is now the nonproprietary name for ATH-1017, as per recommendation from the World Health Organization’s (WHO) International Nonproprietary Names Expert Committee. WHO designated the suffix stem “-meton” as a novel drug class, which is based on targeted positive modulation of HGF/MET.1