Safety, Tolerability, And Efficacy Of NE3107 From A Phase 2, Double-Blind, Placebo-Controlled Study In Levodopa/Carbidopa-Treated Patients With Parkinson’s Disease (P1-11.008)

Abstract

<h3>Objective:</h3> To assess the safety, tolerability, and efficacy of NE3107 in levodopa/carbidopa-treated patients with Parkinson’s disease (PD) over 27 days. <h3>Background:</h3> PD is characterized by the loss of dopaminergic neurons and compromised motor control. Levodopa provides pro-motoric relief but lacks disease-modifying potential and can cause motor complications, including levodopa-induced dyskinesia (LID). Inflammatory pathways comprising extracellular signal-regulated kinase (ERK) and nuclear factor-kappa B form a feed-forward loop with oxidative stress to drive neurodegeneration. NE3107 is an oral, blood-brain barrier–permeable molecule that binds ERK and inhibits pro-inflammatory pathways without affecting homeostatic functions. In a marmoset model of PD, NE3107 treatment improved mobility, enhanced levodopa activity, and decreased LID and neuronal death in the substantia nigra. We initiated a phase 2, double-blind, placebo-controlled study to evaluate the safety, tolerability, efficacy, and pharmacokinetic effects of NE3107 in levodopa/carbidopa-treated patients with PD. <h3>Design/Methods:</h3> Forty patients were planned to be enrolled and randomized 1:1 to receive 20 mg oral NE3107 twice daily or placebo for 27 days. Patients were 30 to 80 years old with a diagnosis of PD, response to levodopa, and bradykinesia. Eligible patients were taking 300 mg levodopa/carbidopa daily and had a history of motor fluctuations with early morning OFF episodes. Safety and tolerability endpoints evaluated treatment-emergent and serious adverse events and suicidality, changes in vital signs, and the percentage of completers. Efficacy endpoints included daily change in The Movement Disorder Society-Sponsored Revision of the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Part III from baseline to post-dose timepoints, MDS-UPDRS Part I and II Scores, and total ON time with or without dyskinesia. <h3>Results:</h3> Outcomes of the efficacy, safety, and tolerability analyses will be presented at the conference. <h3>Conclusions:</h3> Using safety, tolerability, and efficacy analyses, this study aimed to demonstrate the potential therapeutic benefits of NE3107 in levodopa/carbidopa-treated patients with PD. <b>Disclosure:</b> Mr. Ahlem has received personal compensation for serving as an employee of Biovie, Inc.. Mr. Ahlem has received personal compensation in the range of $100,000-$499,999 for serving as an officer or member of the Board of Directors for Biovie, Inc.. Mr. Ahlem has received intellectual property interests from a discovery or technology relating to health care. Dr. Reading has received personal compensation for serving as an employee of Biovie, Inc.. Dr. Reading has received intellectual property interests from a discovery or technology relating to health care. Mr. Djan has received personal compensation for serving as an employee of BioVie Inc.. Dr. Palumbo has received personal compensation for serving as an employee of BioVie. An immediate family member of Dr. Palumbo has received personal compensation for serving as an employee of Merck Research Laboratories. Dr. Palumbo has received personal compensation in the range of $0-$499 for serving as an officer or member of the Board of Directors for BioVie. Dr. Palumbo has stock in BioVie. An immediate family member of Dr. Palumbo has stock in Merck Research Laboratories. Dr. Palumbo has received intellectual property interests from a discovery or technology relating to health care. Dr. Palumbo has received intellectual property interests from a discovery or technology relating to health care. Dr. Palumbo has received intellectual property interests from a discovery or technology relating to health care.