Improvements in daily “on” and “off” times were significantly greater with continuous subcutaneous foslevodopa-foscarbidopa than with oral levodopa-carbidopa.

An investigational soluble formulation of levodopa and carbidopa prodrugs, known as foslevodopa-foscarbidopa, has been suggested as a continuous subcutaneous infusion therapy for patients with advanced Parkinson disease (PD). To assess the safety and efficacy of this approach, investigators in the U.S. and Australia have conducted an industry-funded, multicenter, randomized, double-blind, double-dummy, active-controlled, phase 3 study in which 141 advanced PD patients (with an average daily “off” time of ≥2.5 hours) were assigned to receive continuous subcutaneous infusion of foslevodopa-foscarbidopa plus oral placebo or continuous subcutaneous infusion of placebo plus oral levodopa-carbidopa.

After 12 weeks of treatment, patients who received continuous subcutaneous foslevodopa-foscarbidopa, compared with those who received oral levodopa-carbidopa, had a significantly greater increase in mean “on” time without troublesome dyskinesia (the primary outcome; 2.72 vs. 0.97 hours/day; P=0.0083) and a significantly greater reduction in mean “off” time (−2.75 vs. (−0.96 hours/day; P=0.0054). The most frequent adverse events in the foslevodopa-foscarbidopa group, most of which were of mild-to-moderate severity, were infusion-site erythema in 27%, pain in 26%, cellulitis in 19%, and edema in 12%; one patient experienced catheter-site cellulitis and one experienced infusion-site cellulitis.

Comment

The field has long awaited the arrival of subcutaneous levodopa and carbidopa prodrugs that may be infused subcutaneously. This approach, if FDA-approved, will add to a growing list of options that can be considered prior to the use of more invasive procedures, such as duodenal pumps, deep brain stimulation, or ablative brain therapies.