Pivotal Open-Label Extension Initiated for Alzheimer Drug ATH-1017

Hans Moebius, MD, PhD

Athira Pharma recently announced that they have begun enrolling patients into an open-label extension for its ongoing phase 2/3 LIFT-AD (NCT04488419) and phase 2 ACT-AD (NCT04491006) trials evaluating its investigational agent ATH-1017 for the treatment of mild-to-moderate Alzheimer disease (AD). Topline data of ACT-AD are targeted for early 2022 and topline data from LIFT-AD are targeted by the end of 2022.¹

Following completion of the 26-week treatment period during the LIFT-AD or ACT-AD trials, patients may elect to continue to the open-label extension (NCT04886063) and receive treatment with ATH-1017 at the high dose (70 mg/day) for an additional 26 weeks. ATH-1017, a small molecule therapeutic designed to enhance the activity of the Hepatocyte Growth Factor (HGF) and its receptor, MET, will be evaluated in both a double-blind, placebo-controlled setting. Patients will be stratified 1:1:1 to receive low-dose ATH-1017 (40 mg/day), high-dose ATH-1017 (70 mg/day), or placebo.

"This treatment extension allows us to meet investigator and patient interest in continuing treatment with ATH-1017. We can now collect up to 1 year of safety and efficacy data on ATH-1017, and patients who received placebo during the randomized portion of the trial will now be able to receive up to 26 weeks of therapy,” Hans Moebius, MD, PhD, chief medical officer, Athira, said in a statement.¹ “It’s rewarding to have our first patients completing six months of study now continue their treatment. Our novel treatment approach is agnostic to the underlying disease pathology and is designed to focus on neuronal regeneration, which has the potential to improve clinical outcomes for patients.”

READ MORE: Biopharma Support for Alzheimer Disease Trials Has Decreased In Recent Years

Investigators will assess whether the drug can show meaningful improvement in cognition, global, and functional assessments compared to placebo. Event-related potentials (ERP P300), a functional measure of working memory processing speed and executive function, will be assessed in the 75 patients included in the ACT-AD trial. Additionally, investigators in that study will obtain quantitative electroencephalograms (qEEG) from each individual.

In December 2020, Athira announced it had been rewarded a $15 million grant from the National Institute on Aging (NIA) to support the ACT-AD trial, which came weeks after the initial dosing was announced.² At the time, the company also noted that findings from ACT-AD, such as appropriate dosage, may influence trial methods and outcome measures of LIFT-AD.

"There remains an urgent need for therapies that improve cognition for patients who are living with mild-to-moderate Alzheimer disease,” Michael Mega, MD, PhD, director, Center for Cognitive Health, and a principal investigator of the ACT-AD trial, said in a statement.¹ “The data we will continue to collect in this open label extension could help us to better understand the long-term safety and efficacy profile of ATH-1017 and could help Athira best design future clinical trials of ATH-1017.”

In October 2017, the company began a first-in human, phase 1 safety study of single- and multiple-ascending doses in patients with AD and health controls. Funded by the Alzheimer’s Drug Discovery Foundation and others, the placebo-controlled trial showed that the treatment was generally well tolerated at all tested doses. Measures evaluating brain activity by qEEG also produced a strong suite of translational data. Statistically significant improvements in ERP P300 latency were noted in patients with AD following multiple dose treatments with ATH-1017.

REFERENCES

1. Athira Pharma announces initiation of open-label extension study for LIFT-AD and ACT-AD clinical trials of ATH-1017 for Alzheimer disease. News release. Athira Pharma. July 7, 2021. Accessed July 12, 2021. https://www.globenewswire.com/news-release/2021/07/06/2258079/0/en/Athira-Pharma-Announces-Initiation-of-Open-Label-Extension-Study-for-LIFT-AD-and-ACT-AD-Clinical-Trials-of-ATH-1017-for-Alzheimer-s-Disease.html

2. Athira Pharma awarded $15 million grant from National Institute on Aging to support ACT-AD clinical trial in Alzheimer's disease. News release. Athira Pharma. December 8, 2020. Accessed July 12, 2021. https://www.barrons.com/press-release/athira-pharma-awarded-15-million-grant-from-national-institute-on-aging-to-support-act-ad-clinical-trial-in-alzheimer-s-disease-01607430936?tesla=y&tesla=y