Dosing Starts in Phase 2/3 Trial of Athira’s ATH-1017 for Alzheimer’s

Dosing of patients has begun in a Phase 2/3 clinical trial evaluating ATH-1017, Athira Pharma‘s investigational candidate for the treatment of mild to moderate Alzheimer’s disease.

“Embarking on this trial to evaluate our new approach to treating Alzheimer’s is the start of a collective experience that will involve not only individuals with Alzheimer’s but their caregivers and family members,” Leen Kawas, PhD, president and CEO of Athira, said in a press release.

Called LIFT-AD, the randomized trial (NCT04488419) will evaluate the safety and efficacy of ATH-1017 (previously known as NDX-1017), compared with a placebo, for the treatment of mild to moderate Alzheimer’s disease.

An estimated 300 individuals are currently being recruited for the trial in Florida and Washington; more information can be found here.

Participants will be randomly assigned to receive either a low or high dose of ATH-1017 or a placebo, delivered subcutaneously (under the skin) daily for 26 weeks. Clinical efficacy will be demonstrated by improvement in cognition and functional assessments compared with the placebo.

Secondary objectives include assessing ATH-1017’s effects on cognition as measured by the Alzheimer’s Disease Assessment Scale-Cognitive Subscale, and on patients’ global function as measured by the Alzheimer’s Disease Study Cooperative Study-Clinical Global Impression of Change and Activities of Daily Living.

ATH-1017 is a small molecule specifically designed to increase the activity of the hepatocyte growth factor (HGF, also known as scatter factor), and its receptor protein MET. Known for its role in liver regeneration, several studies have reported that HGF-MET also can regulate various brain functions, including axonal growth — the long projections of nerve cells that allow them to communicate — neuronal survival, and transmission of information between cells (synapses).

Designed to slow or stop disease progression or even reverse it, ATH-1017 was shown to be able to regenerate nerve cells and improve cognitive function in preclinical studies.

Results from a previous Phase 1a/b trial (NCT0329872) showed that the treatment was safe and well tolerated at multiple dose levels in healthy individuals as well as those with amnestic mild cognitive impairment or Alzheimer’s disease.

Moreover, ATH-1017 was capable of crossing the blood-brain barrier — a semipermeable membrane that protects the brain from the outside environment and can hinder the delivery of certain therapies — activating its targets across a range of doses.

Increasing doses of ATH-1017 correlated with improvements in learning and memory as well as cognitive processes.

“Data from our previous study show functional biomarker effects indicating potentially positive effects of ATH-1017 on brain function in Alzheimer’s patient. Our goal is to confirm these compelling effects in a larger ATH-1017 study as there is a significant unmet need for new Alzheimer’s treatments,” said Hans Moebius, MD, PhD, chief medical officer at Athira.