Phase 2 trial of therapy for LRRK2-tied Parkinson's may open soon

25 Nov 2024, 13:00 by Margarida Maia, PhD · Parkinson's News Today

An upcoming Phase 2 clinical trial is due to test NEU-411, a brain-penetrant oral small molecule that Neuron23 is developing to slow the progression of Parkinson’s in people with early-stage disease who carry variations in the LRRK2 gene.

The trial, called NEULARK (NCT06680830), is expected to launch in January and enroll up to 150 adult patients, ages 50 to 80. All will be randomly assigned to 30 mg of NEU-411 or a placebo, taken daily by mouth for 52 weeks or one year. Its goal is to test how safe NEU-411 is and how well it works against the placebo.

Patients will be selected with a test developed in collaboration with Qiagen. The test combines DNA readings to detect variations in LRRK2 with a computer model, working to predict those most likely to produce an overactive version of the enzyme coded by that gene. An overactive LRRK2 enzyme is thought to contribute to Parkinson’s by impairing a cell’s ability to get rid of damaging material.

“The NEULARK trial represents a new dawn in the evolution of Parkinson’s disease research and treatment,” Nancy Stagliano, PhD, Neuron23’s CEO, said in a company press release. “We are on track to initiate this trial early in 2025,” Stagliano added.

LRRK2 mutations are a common cause of familial Parkinson’s

While mutations in LRRK2 are one of the most common genetic causes of familial Parkinson’s, Neuron23 has identified single nucleotide polymorphisms — variations in a single building block of DNA — that make for an overactive LRRK2 in up to 30% of patients with idiopathic Parkinson’s, as the disease is called when its causes are not clear.

NEU-411 is designed to inhibit LRRK2. In Parkinson’s, toxic protein clumps damage and kill dopaminergic neurons, the nerve cells that produce the dopamine that is needed to control movement.

In a placebo-controlled Phase 1 clinical trial (NCT05755191), NEU-411 was found to be safe and well tolerated in single or multiple ascending doses given to over 100 healthy adults for up to 28 days, the company reported.

A main goal or primary endpoint of the NEULARK trial is to watch for changes in a digital biomarker developed by Roche Information Solutions, which focuses on digital health solutions. Such a biomarker is believed to track progression of Parkinson’s motor and nonmotor symptoms more precisely than traditional clinical tools.

Trial patients will show markers that might support treatment benefits

Neuron23 is also collaborating with Sano Genetics, using genetic data to streamline referrals of patients who may be eligible to enter the NEULARK trial.

“By utilizing a digital biomarker as the primary endpoint and the first precision medicine patient stratification approach in Parkinson’s clinical development, we are shedding new light on how we can effectively identify and measure therapeutic impact in people with LRRK2-driven Parkinson’s,” Stagliano said.

These steps “uniquely positions us to identify people with [Parkinson’s] whom we believe are more likely to respond to our potentially best-in-class LRRK2 inhibitor, NEU-411 … [and potentially to] redefine how we conduct trials in Parkinson’s,” said Sam Jackson, MD, Neuron23’s chief medical officer.

The company reported that its upcoming Phase 2 trial will be a global study, but clinical site locations are not yet available.