Foslevodopa/foscarbidopa in Parkinson's disease

Foslevodopa/foscarbidopa, is a formulation of levodopa/carbidopa phosphate prodrugs (1)

• by generating prodrugs of levodopa and carbidopa the solubility is increased by > 100-fold which allows for a highly concentrated foslevodopa/foscarbidopa solution and enables its administration through a minimally invasive subcutaneous (SC) infusion
• upon delivery to the body, foslevodopa/foscarbidopa is quickly and almost completely metabolized to levodopa/carbidopa by alkaline phosphatases
• continuous subcutaneous infusion (CSCI) of foslevodopa/foscarbidopa alone can achieve high sustained and steady-state therapeutic levels of plasma

NICE state with respect to oslevodopa-foscarbidopa for treating advanced Parkinson’s with motor symptoms:

• foslevodopa–foscarbidopa is recommended as an option for treating advanced levodopa-responsive Parkinson's in adults whose symptoms include severe motor fluctuations and hyperkinesia or dyskinesia, when available medicines are not working well enough, only if:
  • they cannot have apomorphine or deep brain stimulation, or these treatments no longer control symptoms, and
  • the company provides foslevodopa-foscarbidopa according to the commercial arrangement
• the NICE committee noted that:
  • "..Treatment for advanced levodopa-responsive Parkinson's includes adding apomorphine, deep brain stimulation or levodopa–carbidopa intestinal gel to standard care (such as oral levodopa–carbidopa). Foslevodopa-foscarbidopa is given as a continuous infusion under the skin (subcutaneous)...
  • Evidence from a clinical trial suggests that foslevodopa–foscarbidopa improves motor symptoms compared with standard care. But some people in the trial had previously had apomorphine, so it is uncertain how well foslevodopa–foscarbidopa works for people who cannot have apomorphine. An indirect comparison suggests that foslevodopa–foscarbidopa works as well as levodopa–carbidopa intestinal gel, but the results are uncertain.."

Reference:

1. Rosebraugh M, Liu W, Neenan M, Facheris MF. Foslevodopa/Foscarbidopa Is Well Tolerated and Maintains Stable Levodopa and Carbidopa Exposure Following Subcutaneous Infusion. J Parkinsons Dis. 2021;11(4):1695-1702.
2. NICE (November 29th 2023). Foslevodopa-foscarbidopa for treating advanced Parkinson’s with motor symptoms