ATH-1105 experimental therapy found safe in healthy adults: Trial
Clinical trial testing ATH-1105 in ALS patients launching later this year
ATH-1105, an experimental oral therapy for amyotrophic lateral sclerosis (ALS) and other neurodegenerative diseases, was found to be safe and well tolerated in healthy volunteers, according to the treatment’s developer, Athira Pharma.
The data comes from a first-in-human Phase 1 trial (NCT06432647) that tested the safety and pharmacological properties of single and multiple ascending doses of the medication in 80 healthy adults.
New clinical trial to determine ATH-1105’s effects on nerve damage biomarker
Based on the findings, Athira is planning to launch a clinical trial in ALS patients later this year, which will determine ATH-1105’s effects on a validated biomarker of nerve damage called neurofilament light chain (NfL).
“We are very encouraged by these first-in-human safety and pharmacokinetic data and how they reinforce ATH-1105’s continued development as a potential treatment for ALS,” Javier San Martin, MD, chief medical officer at Athira, said in a company press release.
Results from the Phase 1 trial were shared by Athira at the recent ALS Drug Development Summit in Boston, in an oral presentation titled “Advancing ATH-1105 for ALS Through Early Clinical and PK Data.”
The company also presented data from animal experiments in the poster “ATH-1105 Enhances Motor Neuron Survival and Reduces TDP-43 Pathology in Preclinical ALS Models.”
ALS is a neurodegenerative condition where motor neurons, the nerve cells that control muscle movement, gradually sicken and die. ATH-1105 is a small molecule designed to target multiple mechanisms involved in ALS progression, including inflammation and neurodegeneration.
It works by activating a signaling pathway called the hepatocyte growth factor (HGF) system, which is important for the maintenance and health of nerve cells. In animal models, ATH-1105 has been shown to improve motor and nerve function and to reduce markers of inflammation and nerve cell death, the company notes on its website.
Athira’s recently completed study involving healthy volunteers examined the safety of ATH-1105 and its pharmacokinetics, or how it moves into, through, and out of the body.
The study was conducted in two parts. In part A, participants received a single dose of ATH-1105 or a placebo, as an oral solution, while part B involved daily treatment with the active medication or a placebo for 10 days. In each part, each group received a larger dose than the group before.
ATH-1105 able to reach brain, spinal cord
Researchers have now announced that ATH-1105 was safe and well tolerated during both the single and multiple ascending phases of the trial.
Pharmacokinetics depended on the dose participants received. One outcome of interest was how well the treatment penetrated the central nervous system, which includes the brain and spinal cord. The drug was able to reach the brain and spinal cord, with levels dependent on the dose of the medication.
While efficacy data in humans aren’t available yet, the therapy showed “consistent and robust clinical benefits” in various animal models of ALS. Mice treated with ATH-1105 experienced less neurodegeneration and inflammation, had reduced accumulation of toxic protein clumps (a hallmark of ALS), and also survived significantly longer compared with untreated mice.
“We look forward to enabling the initiation of a clinical trial in ALS patients in late 2025 and to evaluating ATH-1105’s effect on an ALS validated biomarker (NfL),” San Martin said.
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