Phase 2/3 Trial of ATH-1017 for Mild or Moderate Alzheimer’s Enrolling

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by Patricia Inacio PhD |

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Athira Pharma announced its Phase 2 ACT-AD trial is fully enrolled and its Phase 2/3 LIFT-AD trial has reached more than half of its target number. Both studies are evaluating the safety and efficacy of ATH-1017 in people with mild to moderate Alzheimer’s disease.

Eligible adults, ages 55 to 85, are still being recruited for the LIFT-AD trial (NCT04488419) taking place across the U.S. It aims to enroll 300 patients; contact and site information is available here.

Top-line data from the ACT-AD trial (NCT04491006) are likely to be available by mid-year. Its primary goal is to assess event-related potential (ERP), which evaluates working memory processing speed and executive function. Secondary goals include improvements in cognition and global and functional assessments.

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“We expect data read out from the ACT-AD trial … in the first half of 2022. These results will provide important insights into ATH-1017’s treatment effects in Alzheimer’s disease,” Hans Moebius, MD, PhD, Athira’s chief medical officer, said in a press release.

Moebius shared these updates at the 2021 Clinical Trials on Alzheimer’s Disease (CTAD) Conference, held Nov. 9–12 in Boston, in the presentation, “Phase 2/3 trials of ATH-1017, a novel treatment approach for mild-to-moderate Alzheimer’s disease: updates and baseline data.”

ATH-1017 is a small molecule designed to enhance the effect of hepatocyte growth factor (HGF) and its receptor, MET. Both are found in the central nervous system (brain and spinal cord).

When bound to its receptor, HGF promotes cell growth, cell migration, and blood vessel formation. Enhancing the activity of this signaling pathway is expected to improve brain health and function.

In both trials — the larger LIFT-AD and ACT-AD — patients are randomly assigned to either ATH-1017 at low-dose (40 milligrams/day), ATH-1017 at high-dose (70 mg/day), or to a placebo for 26 weeks (about six months). Both doses of ATH-1017 are given as a subcutaneous (under-the-skin) injection.

All 75 patients (mean age, 71.6) enrolled in ACT-AD at data cutoff have been dosed. Five people discontinued the study, and 10 have finished with their assigned dosing.

In the LIFT-AD trial, 166 patients (mean age, 72.5) currently have been dosed, 22 have left the study, and 22 completed their assigned dosing.

This trial’s primary goal is the overall effect of ATH-1017 as reflected by the Global Statistical Test, an algorithm that combines cognition scores measured using the Alzheimer’s Disease Assessment Scale-Cognitive Subscale (ADAS-Cog11) and the Alzheimer’s Disease Study Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC).

Characteristics of patients in the two trials are similar, the company stated in its release, and their disease severity matches that of a prior Phase 1b trial, which showed ATH-1017 significantly improved ERP scores.

People in that earlier trial “showed a statistically significant benefit in Event-Related-Potential (ERP) P300 latency, a functional measure of working memory processing speed. We are encouraged by the safety profile to-date and low early termination rates from both studies as well as the rate of enrollment,” Moebius said.

Patients who complete either the ACT-AD or LIFT-AD trials are eligible to enroll in Athira’s open-label extension trial (NCT04886063) and receive ATH-1017 at the high dose for an additional 26 weeks.

“We are extremely grateful to the community of patients and researchers participating in this program and sincerely appreciate all that they have done to get us to this point,” said Mark Litton, PhD, Athira’s president and CEO.

“Regardless of the root cause of Alzheimer’s disease, a therapy that has potential to target the cognitive symptoms caused by neurodegeneration is needed to address the unmet patient need, and ATH-1017 has the potential to meet that need,” Litton added.