Phase 2 Trial Planned for KM-819 as Disease-modifying Therapy
This follows the approval by the U.S. Food and Drug Administration of Fascinate’s request for such a trial, in the form of an investigational new drug (IND) application.
The study is designed to evaluate the disease-modifying potential of KM-819 in slowing or halting Parkinson’s progression in people with early and midstage disease, including GBA mutation carriers, the company announced in a press release.
Nerve cell damage in Parkinson’s disease is caused by the buildup of toxic forms of the protein alpha-synuclein. The nerve cells most affected are those that produce the neurotransmitter dopamine, a chemical messenger essential for muscle control.
Genetic errors, such as in the mutations in GBA1 gene, lead to the buildup of toxic alpha-synuclein, among other proteins, inside nerve cells, which can drive Parkinson’s development.
KM-819 is a molecule given by mouth that inhibits FAF1, a protein found at higher levels in Parkinson’s patients. It works by promoting apoptosis, or regulated cell death.
By inhibiting FAF1, KM-819 is thought to prevent the death of dopaminergic neurons and potentially slow or stop Parkinson’s progression.
In preclinical studies, KM-819 showed superior effectiveness in neuroprotection in cell models and in protecting dopaminergic neurons in animal models of Parkinson’s disease. The therapy also has been shown to improve behavioral tests given the animals.
In a previous Phase 1 clinical trial (NCT03022799) in healthy volunteers, the medication showed a strong safety profile.
The goal of the Phase 2 trial is to evaluate the safety, tolerability, and pharmacokinetics — the way medication is processed within the body — and preliminary efficacy of KM-819 at differing doses.
It will be placebo-controlled and divided into two parts. Part 1 will assess the safety and pharmacokinetics of escalating doses of KM-819. This will be followed by part 2, a two-year treatment of patients at the selected doses to evaluate the therapy’s safety and early efficacy.
“We are excited about the prospect of KM-819 for Parkinson’s disease with Phase 2 trials looking for evidence of disease modifying effects. KM-819 shows a promising neuroprotection efficacy in dopaminergic cells including GBA mutation, as well as clearing the alpha-synuclein,” the company stated.