Foslevodopa/Foscarbidopa: A New Subcutaneous Treatment for Parkinson's Disease. Issue 1 (4th May 2021)

• Record Type: Journal Article
• Authors: Rosebraugh, Matthew; Voight, Eric A.; Moussa, Ehab M.; Jameel, Feroz; Lou, Xiaochun; Zhang, Geoff G. Z.; Mayer, Peter T.; Stolarik, Deanne; Carr, Robert A.; Enright, Brian P.; Liu, Wei; Facheris, Maurizio F.; Kym, Philip R.
• Is Part Of: Annals of neurology. Volume 90:Issue 1(2021)
• Page Start: 52
• Page End: 61
• Publication Date: 2021-05-04
• Subjects: Neurology -- Periodicals; Pediatric neurology -- Periodicals; Nervous system -- Surgery -- Periodicals; 616.8
• DOI: 10.1002/ana.26073
• Languages: English
• ISSNs: 0364-5134

Abstract

Abstract : 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;90:52–61