24-Hour Subcutaneous Infusion Foslevodopa/Foscarbidopa Improves Advanced PD

Continuous subcutaneous infusion of foslevodopa/foscarbidopa demonstrates a favorable safety and tolerability profile for patients with advanced Parkinson disease (PD), according to study findings published in Neurology and Therapy.

The gold standard of treatment for PD consists of oral formulations of levodopa and carbidopa, with adequate control of motor symptoms seen in the early stages of disease. However, as plasma concentration directly influences symptom control, individuals are often subject to disabling motor fluctuations over the course of the disease, due to the nature of oral formulations (e.g., short half-life). Expanding on a prior 12-week clinical trial, researchers conducted a separate 52-week open-label study to assess the efficacy and tolerability of a 24-hour/day continuous subcutaneous injection of foslevodopa/foscarbidopa in patients with advanced PD.

The researchers conducted the phase 3, multi-center study (ClinicalTrials.gov Identifier: NCT03781167) at 60 sites across 13 countries with an initial enrollment of 244 individuals between June 2019 and August 2021. Inclusion criteria included individuals aged 30 and older with 2.5 hours/day or more of “off” time (i.e., periods of poor mobility, slowness, etc.), documented over an electronic PD diary. Patients with any significant skin conditions that could interfere with the assessment of the infusion site were excluded from the study.

Patients received hourly infusions of foslevodopa/foscarbidopa (700-4250 mg of levodopa per 24 hours) for 1 year. Dosing started on day 1 and follow-up visits were planned for day 2, weeks 1-4, 6, 13, 26, 39, and 52.

Primary outcome of the study was safety/tolerability of continuous subcutaneous injection, secondary outcomes included proportion of patients reporting akinesia, changes in baseline “off” time, as well as sleep and movement ratings, defined by various reporting scales (Movement Disorder Society Unified Parkinson’s Disease Rating Scale [MDS-UPDRS] and Parkinson’s Disease Sleep Scale–2 [PDSS-2]).

Of the 244 patients enrolled in the study, 137 completed the 52-week study treatment. The majority of those enrolled were White (84.8%), with a mean age of 63.9 years and an average duration of PD diagnosis of 10.7 years.

A majority of patients (94.3%) experienced at least 1 adverse effect; however, the majority were non-serious, including infusion erythema (52%), nodule (28.7%), cellulitis (23.0%), pain (15.6%) and abscess (11.1%). Most events resolved over a median duration of 12.0 days. No clinically relevant changes from baseline of any laboratory parameters, vital signs, or electrocardiogram values were found throughout the course of the study.

At week 52, the researchers noted a mean (SD) change from baseline in “off” time of -3.5 hours (P ≤0.001), indicative of a reduction of an average of 59% spent in “off” time. “On” time (i.e., good motor system control) was shown to increase from baseline to week 52 by a mean (SD) of 3.8 hours, translating to a 41% increase of time without troublesome dyskinesia.

About 50% fewer patients reported morning akinesia at week 52, when compared to baseline, a decrease from 77.7% to 27.8%.

Notably, the researchers also found improvement in PDSS-2, as well as improvement of actives of daily living, body discomfort and bodily discomfort, as noted from the EuroQol 5-dimension questionnaire (EQ-5D-5L). At week 52, the researchers also saw symptom improvement in part II and IV (motor aspects of daily living, motor complications) of MDS-UPDRS (P ≤0.001 for both).

A study limitation included not accounting for patients who prematurely discontinued the trial in the efficacy analysis.

“Overall, by providing individualized, continuous, 24-hour/day, subcutaneous delivery of LD [levodopa] and CD [carbidopa] prodrugs, foslevodopa/foscarbidopa has the potential to provide an efficacious and safe nonsurgical alternative therapy to other currently available treatments for controlling fluctuations and improving QoL [quality of life] in patients with aPD [advanced PD],” the researchers concluded.

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