Foslevodopa/Foscarbidopa: A New Subcutaneous Treatment for Parkinson's Disease

Objective The aim was to demonstrate that continuous s.c. infusion of a soluble levodopa (LD)/carbidopa (CD) phosphate prodrug combination effectively delivers stable LD exposure via a minimally invasive and convenient mode and has the potential to treat Parkinson's disease (PD) patients who are not well controlled on oral medication. Methods Foslevodopa and foscarbidopa were prepared and the equilibrium solubility and chemical stability examined in aqueous media with different values of pH. Solutions of foslevodopa/foscarbidopa (ratios ranging from 4:1 to 20:1) were prepared by dissolving pH-adjusted lyophilized materials in water and infused s.c. in healthy volunteers for <= 72 hours. Frequent blood samples were collected to measure LD and CD exposure, and safety was monitored throughout the study. Results Foslevodopa/foscarbidopa (ABBV-951) demonstrates high water solubility and excellent chemical stability near physiological pH, enabling continuous s.c. infusion therapy. After s.c. infusion, a stable LD pharmacokinetic (PK) profile was maintained for <= 72 hours, and the infusion was well tolerated. Interpretation Preparation of foslevodopa and foscarbidopa enables preclinical and clinical PK, safety, and tolerability studies in support of their advancement for the treatment of PD. In phase 1 clinical trials, foslevodopa/foscarbidopa demonstrates consistent and stable LD plasma exposure, supporting further studies of this treatment as a potentially transformational option for those suffering from PD. ANN NEUROL 2021

Automated summary

This study demonstrates the effectiveness of continuous subcutaneous infusion of a soluble levodopa/carbidopa phosphate prodrug combination in delivering stable levodopa exposure, potentially treating Parkinson's disease patients who are not well controlled on oral medication. The prepared drugs show high water solubility, excellent chemical stability, and good tolerability in both animals and healthy volunteers. The prepared combination supports further clinical studies as a potentially transformative option for Parkinson's disease treatment.