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Advancing the Treatment of Motor Fluctuations in Parkinson’s Disease with a Next-Generation Levodopa/Carbidopa Formulation

Year: 2026

Type: article

Abstract: As of today, levodopa remains the cornerstone of symptomatic management in Parkinson's disease (PD). As PD progresses, the limitations of immediate-release (IR) levodopa/carbidopa, such as its short half-life and inconsistent absorption, result in unstable fluctuating levodopa plasma concentrations. These fluctuations contribute to motor complications including wearing off, delayed ON responses, and dyskinesias. To maintain symptom control, patients often require frequent dosing or, eventually, transition to device-aided therapies (DATs). Although effective, these therapies are invasive and require intensive clinical monitoring. IPX203, a next-generation modified-release (MR) levodopa/carbidopa formulation, may address these challenges. Approved by the US Food and Drug Administration (FDA) in 2024, IPX203 combines IR granules and extended-release (ER) pellets within a single capsule. IPX203 is designed to improve levodopa delivery and absorption, enhancing therapeutic benefit. It ensures both rapid onset and sustained levodopa plasma concentrations, minimising peak-to-trough fluctuations and reducing dosing frequency. The formulation delivers 100% of the carbidopa and 25% of the levodopa dose via IR granules, while the remaining 75% of levodopa is gradually released from ER pellets engineered with sustained release, mucoadhesive, and enteric coatings to optimise proximal small intestinal absorption. Clinical studies have shown that IPX203 significantly reduces OFF time, increases Good ON time, and improves motor symptom control compared with IR levodopa/carbidopa. It may also extend symptom relief into the following morning. This review outlines the pharmacological rationale and clinical evidence supporting IPX203 therapy, highlighting its potential to enhance motor control and improve patients' quality of life, thereby supporting a more personalised and sustained approach to PD management.

Source: Neurology and Therapy

DOI: 10.1007/s40120-026-00898-z

Authors: Fabrizio Stocchi, Mathias Knecht, Ivan Marjanovic, Achim Wach, Jaakko Kopra, Jaime Kulisevsky