Neuron23 Inc. has announced the launch of its groundbreaking Phase 2 NEULARK clinical trial, marking a significant advancement in precision medicine for Parkinson's disease. The global, double-blind, placebo-controlled study will evaluate NEU-411, a brain-penetrant, potent and selective LRRK2 inhibitor, in people with early-stage Parkinson's disease, with trial initiation planned for early 2025.
The trial represents a paradigm shift in Parkinson's disease research by utilizing a state-of-the-art digital biomarker developed by Roche Information Solutions as the primary endpoint, replacing traditional clinical rating scales that are typically assessed every 8-12 weeks. This smartphone-based solution will frequently measure PD symptoms such as slowed movement and tremor, as well as non-motor symptoms including cognition, providing significantly greater frequency of data measurement and more objective quantification of symptoms.
"The NEULARK trial represents a new dawn in the evolution of Parkinson's disease research and treatment. With no therapies currently available that impact the underlying disease progression of Parkinson's, existing options are limited to alleviating symptoms," said Nancy Stagliano, Ph.D., Chief Executive Officer of Neuron23.
Targeting LRRK2-Driven Disease
NEU-411 specifically targets LRRK2-driven Parkinson's disease, which Neuron23 estimates affects up to 30% of people with PD. While LRRK2 mutations are the most common cause of familial PD, representing 2% of the patient population, emerging evidence suggests that LRRK2 activity may play a role in a broader subset of patients with idiopathic PD.
Neuron23 has identified single-nucleotide polymorphisms (SNPs) that are predicted to drive LRRK2 overactivity in up to 30% of people with idiopathic PD. People with PD who have these SNPs, together with those who have LRRK2 gene mutations, make up the population collectively referred to as LRRK2-driven PD and represent who the company believes is most likely to benefit from LRRK2 inhibition.
In Phase 1 clinical trials, NEU-411 demonstrated safety and tolerability in over 100 healthy volunteers for up to 28 days, with robust target engagement of the LRRK2 pathway using fluid-based biomarkers.
Precision Medicine Patient Stratification
The NEULARK trial will employ an investigational clinical trial assay developed in collaboration with QIAGEN to select people with LRRK2-driven PD. This assay leverages whole exome next-generation sequencing (NGS) to detect Neuron23's selected panel of SNPs and an algorithmic predictive model to define people who are likely to have elevated LRRK2 pathway activity.
Under an exclusive agreement, Quest Diagnostics will deploy the assay at its advanced diagnostics laboratory in San Juan Capistrano, California, to identify trial candidates. This screening process is designed to maximize the likelihood of enrolling people who have the highest potential for benefit from treatment with NEU-411.
Neuron23 has also partnered with Sano Genetics to streamline patient referrals through saliva test kits that can identify people with LRRK2-driven PD, providing genetic counseling and engagement tools including tailored educational content.
Digital Biomarker Innovation
The collaboration with Roche represents a significant technological advancement in clinical trial methodology for neurodegenerative diseases. The navify digital biomarker solution has been designed based on extensive clinical and observational data in PD patients, providing valuable insights into disease progression while reducing patient burden through fewer in-clinic visits.
"By integrating an advanced digital biomarker developed by Roche Diagnostics, the NEULARK trial has the potential to set a new benchmark for monitoring Parkinson's disease progression with unprecedented resolution and precision," said Sam Jackson, M.D., Chief Medical Officer of Neuron23.
Clinical development in PD has historically been challenged by symptom variability that reduces the sensitivity and reliability of clinical outcome assessments. The digital biomarker approach aims to address these limitations by providing continuous, objective monitoring of disease progression.
Addressing Unmet Medical Need
Parkinson's disease is a brain disorder that causes unintended or uncontrollable movements, including shaking, stiffness and difficulty with balance and coordination. Symptoms usually begin gradually and worsen over time, with additional symptoms including mental and behavioral changes, sleep problems, depression, memory difficulties and fatigue.
Currently, there is no cure or therapy that impacts underlying disease progression available for PD, with treatment options limited to alleviating symptoms. By specifically inhibiting the overactive LRRK2 kinase pathway, NEU-411 aims to address an underlying cause of disease progression in people with LRRK2-driven PD, offering a more precise and potentially more effective approach compared to existing treatment options.
The NEULARK trial (NCT06680830) serves as a major value-creating catalyst for continued innovation across Neuron23's neuroimmunology pipeline, representing the company's most advanced clinical program in its focus on developing precision medicines for genetically defined neurological and immunological diseases.
