Foslevodopa/Foscarbidopa Improves Morning Akinesia, Motor Fluctuations in PD

Among patients with advanced Parkinson disease (PD) treated with foslevodopa/foscarbidopa (LDp/CDp), improvement in morning akinesia is strongly associated with clinically meaningful benefits in motor fluctuations, activities of daily living (ADL), and quality of life (QoL). These are the results of a study presented at the 2025 American Academy of Neurology (AAN) annual meeting, held from April 5 to 9, 2025, in San Diego, California.

In a series of 3 clinical trials, including a 12-week, active-controlled, double-blind trial (ClinicalTrials.gov Identifier: NCT04380142); a 52-week, single-arm, open-label trial (ClinicalTrials.gov Identifier: NCT03781167); and a 96-week open-label extension trial (ClinicalTrials.gov Identifier: NCT04750226), researchers assessed the association between morning akinesia and motor complications, ADL, sleep, and QoL in patients with advanced PD receiving continuous subcutaneous infusion of LDp/CDp. Participants enrolled in these studies were patients with advanced PD who had a history of morning akinesia, a motor complication frequently seen in individuals with the disease, often impacting their ability to carry out daily tasks and significantly decreasing their QoL.

The study included a total of 93 patients, all with baseline morning akinesia. The researchers compared 2 distinct patient groups: those who transitioned to waking in an “ON” state, without morning akinesia, and those who continued to experience morning akinesia upon waking after 12 weeks of treatment.

The researchers found that a significant proportion of patients (n=69; 74.2%) transitioned to the “Without Morning Akinesia” group, showing clinically meaningful improvements in key outcomes such as increased “ON” time without dyskinesia, reduced “OFF” time, better ADL scores (measured by the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale Part II), and improved QoL as assessed by the PDQ-39 Summary Index.

The improvements were particularly significant for patients who woke in the “ON” state. For example, in the “Without Morning Akinesia” group, the mean change from baseline for “ON” time without dyskinesia was 5.2 hours, compared to just 1.8 hours in the “Continued Morning Akinesia ” group (P <.001). The “Without Morning Akinesia” group also showed a significant reduction in “OFF” time (-4.4 hours vs -0.2 hours, P <.001) and an improvement in ADL (-4.5 vs. 0.2, P <.01) and QoL (-9.2 vs. -1.0, P <.05).

In addition to these improvements, the “Without Morning Akinesia” group also showed a numerically higher but not statistically significant improvement in the PDSS-2 Total Score, a measure of sleep quality.

Safety data from previous studies indicated that LDp/CDp was generally well tolerated, with no major safety concerns reported.

The researchers noted that the observed improvements in motor function and QoL among patients waking in the “ON” state provide strong evidence supporting the efficacy of LDp/CDp for managing morning akinesia and its associated symptoms.

“Patients receiving LDp/CDp who changed to waking in the “ON” state experienced: more “ON” Time and less “OFF” Time throughout the day, improved QoL, and increased ability to participate in ADL,” the researchers concluded.

Multiple study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.