Objective: To evaluate the motor effects of NE3107 treatment in patients with levodopa-treated Parkinson’s disease (PD) experiencing motor fluctuations.

Background: NE3107 is an oral, blood-brain barrier–permeable molecule that binds extracellular signal-regulated kinase (ERK) in pathology-specific signaling pathways. It inhibits ERK activation and downstream inflammatory cascades, without affecting homeostasis. In animal models of PD, NE3107 treatment was associated with improved motor function, reduced dyskinesia, and increased survival of dopaminergic neurons. We conducted a phase 2a, double-blind, placebo-controlled study to evaluate the safety, tolerability, efficacy, and pharmacokinetics (PK) of NE3107 in carbidopa/levodopa (C/L)-treated patients with PD.

Method: Forty patients aged 30 to 80 years old with a diagnosis of PD, a marked response to levodopa, and a history of motor fluctuations with early morning OFF episodes were enrolled. Patients were randomized 1:1 to receive either 20 mg oral NE3107 twice daily or matching placebo for 28 days. All patients received their usual C/L regimen and adjunctive PD medications. Efficacy endpoints included Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Parts I, II, and III scores. Motor state OFF, ON, and dyskinesia data were collected during the study visits.

Results: Twenty patients received NE3107 + C/L, and 19 patients received placebo + C/L. One patient voluntarily withdrew from the study. After 28 days of treatment, patients who received NE3107 + C/L experienced greater improvements (3+ points) in their MDS-UPDRS Part III (motor) score, compared to patients who received only C/L, at the 2- and 3-hour marks post treatment. Patients <70 years old treated with NE3107 + C/L saw improved morning Part III scores in the practically-defined OFF state, compared to patients treated with only C/L. Six patients in the NE3107 + C/L arm were assessed as being in the ON state on day 28 prior to receiving their morning medication, compared to none of the patients in the placebo + C/L arm (p=0.02).

Conclusion: Our data indicate that NE3107 may improve motor function in levodopa-treated patients with PD, consistent with the preclinical findings. These data support further clinical investigation of NE3107 in PD.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/a-randomized-phase-2a-double-blind-placebo-controlled-clinical-trial-with-ne3107-adjunctive-to-carbidopa-levodopa-in-patients-with-parkinsons-disease/