1st patient dosed in Phase 2 trial of Parkinson’s therapy VTX3232
Connecticut-based study recruiting patients with early Parkinson’s
The first patient with early Parkinson’s disease has been dosed in Ventyx Biosciences‘ Phase 2a clinical trial of Parkinson’s therapy VTX3232, an oral medication designed to reduce inflammation by blocking the activity of the NLRP3 protein.
The trial is still recruiting patients at its single site in New Haven, Connecticut. Top-line data are expected in 2025.
“We are excited to initiate this trial of VTX3232 in patients with early Parkinson’s disease,” Mark Forman, MD, PhD, Ventyx’s chief medical officer, said in a company press release. “There is a compelling body of evidence” supporting the mechanism behind the treatment, he said.
The clinical trial, an open-label study (NCT06556173), aims to assess the safety and tolerability of VTX3232 in an estimated 10 people with early-stage, idiopathic (of unknown cause) Parkinson’s disease, who have never received deep brain stimulation. Patients will receive the oral therapy for 28 days and will be followed for 14 days.
The trial also will assess the Parkinson’s therapy’s pharmacokinetics, or the movement of a medicine into, through, and out of the body, and pharmacodynamics, or its effects on the body, as well as the impact on disease biomarkers. In addition, PET imaging will explore the activation of microglia, the resident immune cells in the brain, which are thought to play a key role in brain inflammation in the context of Parkinson’s. PET imaging uses radioactive molecules, or tracers, to help visualize tissues and organs within the body.
“These measures may provide early insights into the potential of VTX3232 to disrupt Parkinson’s disease” processes, Forman said.
Parkinson’s therapy targets NLRP3
VTX3232 is an NLRP3 inhibitor that could potentially be used for neuroinflammatory and neurodegenerative conditions including Parkinson’s, Alzheimer’s disease, and multiple sclerosis, according to Vertex.
The NLRP3 protein is a component of the inflammasome, a multi-protein complex that when activated triggers a potent inflammatory response, with cells releasing an inflammatory signaling molecule called interleukin-1 beta to help fight off infections.
Evidence suggests that in Parkinson’s, the NLRP3 inflammasome promotes inflammation in the brain and contributes to disease progression. VTX3232 is expected to provide benefits against these processes by blocking NLRP3 in the central nervous system (the brain and spinal cord).
In a Phase 1 study with healthy adult volunteers, VTX3232 was overall well tolerated, with no serious side effects reported.
Analysis of the cerebrospinal fluid (CSF), the liquid that surrounds the brain and spinal cord, was available for certain participants. Data showed that VTX3232, when administered at a dose of 3 mg/day, reached sufficient levels in the blood and CSF to reduce IL-1beta production by at least 50%. A reduction of 90% or more was seen when the dose increased to 40 mg/day.
About the Author
