Parkinson Disease Agent KM-819 Demonstrates Safe Profile in Phase 2 Study

According to a recent announcement, Part 1A, the initial stage of a phase 2 study (NCT05670782) assessing FAScinate Therapeutics’ Parkinson disease (PD) candidate KM-819, was successfully completed, with the therapy showing a favorable safety profile.¹

In its statement, the company said, “We are pleased with the prospects of KM-819 as a disease-modifying treatment for Parkinson’s disease as we progress through Phase 2 trials. Part 1a showed favorable safety even at very high doses, and we are excited to now initiate Part 1b. KM-819 shows great promise when it comes to the neuroprotection of dopaminergic cells, including GBA mutation, as well as in clearing alpha-synuclein."¹

In November 2021, FAScinate announced that the investigational new drug application for the phase 2 trial of KM-819 had been cleared by the FDA.² Part 1A of the 2-part study, initiated in July 2022, assessed the pharmacokinetics and safety of the drug in a dose-escalating fashion in a cohort of healthy elderly individuals. Patients received doses of either 400 mg, 600 mg, or 800 mg of KM-819 or matching placebo once-daily for 7 days, after fasting for 2 hours prior to the administration of treatment. The primary outcome measure was safety, as evaluated through number of adverse events (AEs) and serious AEs.

The subsequent stage, part 1B, is a dose-finding study that will assess 3 doses, including a high dose tested in healthy individuals, in patients with PD. Those findings will be used to select the doses used for the main Part 2 study, a 24-month trial of the selected doses assessing both efficacy and safety end points of PD progression. In Part 2 of the trial, investigators will use change from baseline in Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Part II Activities of Daily Living (ADL) at day 730 as the primary end point.

READ MORE: Inconsistency Identified in Techniques Used to Assess Subjective Cognitive Complaints in Parkinson Disease

In the phase 2 trial, eligible patients are above 40 years old, have a clinical diagnosis of idiopathic PD, and have a Hoehn and Yahn stage score of less than 4. These individuals also have a history or current use of dopamine/dopaminergic drugs, levodopa with decarboxylase inhibitor or dopaminergic agonists, with a stable dosage for at least 30 days before screening. Individuals with a history of levodopa-induced motor fluctuations or dyskinesia, as well as those with cognitive decline, defined by Montreal Cognitive Assessment scores less than 25 for the heathy population and 21 for the patient population, were excluded.

KM-819 is a small molecule inhibitor of Fas-associated factor 1 (FAF1), a key regulatory protein in cell death pathways, that targets various degenerative diseases, including multiple system atrophy. In a previous phase 1 clinical trial (NCT03022799) in healthy volunteers, the medication showed a strong safety profile.³

In that analysis, a total of 88 individuals were enrolled 66 of which received KM-819 and 22 on placebo. After a single dose, the KM-819 plasma exposure showed a less than dose-proportional increase across a dose range of 10 to 400 mg. After repeated dosing, the plasma exposure increased in an appropriately dose-proportional manner across the evaluated dose range of 30 to 400 mg once daily for 7 days.

When administered to the elderly population, KM-819 plasma exposure increased by 102% after a 200 mg once daily dosing for 7 days. The therapy was generally well tolerated, with no treatment-related effects on estimated pharmacodynamic variables observed.

REFERENCES
1. FAScinate Therapeutics completes part 1a of phase 2 study of company’s Parkinson’s disease drug candidate “KM-819.” News release. January 12, 2023. Accessed January 23, 2023. https://www.fascinatetherapeutics.com/news/fascinate-therapeutics-completes-part-1a-of-phase-2-study-of-companys-parkinsons-disease-drug-candidate-km-819
2. FAScinate Therapeutics cleared for phase 2 clinical trials of company’s Parkinson’s disease treatment with approval from US Food and Drug Administration. News release. November 17, 2021. Accessed January 23, 2023. https://www.prweb.com/releases/fascinate_therapeutics_inc_cleared_for_phase_2_clinical_trials_of_companys_parkinsons_disease_treatment_with_approval_from_u_s_food_and_drug_administration/prweb18340255.htm
3. Shin W, Lim KS, Kim MY, et al. A first-in-human study to investigate the safety, tolerability, pharmacokinectics, and pharmacodynamics of KM-819 (FAS-associated factor 1 inhibitor), a drug for Parkinson’s disease, in healthy volunteers. Drug Des Devel Ther. 2019;29(13):1011-1022. doi:10.2147/DDDT.S198753