Levodopa-Carbidopa Infusions for Treatment of Motor Fluctuations in Parkinson’s Disease

A prodrug formulation of levodopa-carbidopa delivered as an intestinal gel (LCIG) (Duopa; Abbvie, Chicago, IL) is approved by the Food and Drug Administration (FDA) for treatment of motor fluctuations and dyskinesia in advanced Parkinson’s disease (PD). Interim analyses of data from a multisite international prospective study (NCT02611713) confirm that treatment with LCIG decreases “OFF” time (mean decrease -4.1 hours from baseline over 12 months). Dyskinesia was also reduced, as measured by a -12.7-point decrease from baseline on Unified Dyskinesia Rating Scale (UDysRS), and this decrease was maintained over a 12-month period. Participants in this study were mostly age 65 or more (78%) and over half (51%) had PD for 10 or more years. 

Meta-analysis of 27 studies (4 clinical trials and 23 observational studies) evaluating 1,562 people with advanced PD who were treated with LCIG shows improvement in PD-related quality of life measure sustained for up to 2 years after beginning treatment.

Despite the efficacy of LCIG on motor symptoms and quality-of-life outcomes, usage can be limited by the need to use a feeding tube (percutaneous endoscopic gastrostomy [PEG]) for delivery. To address this challenge, the manufacturer is also developing a formulation of the prodrug for levodopa-carbidopa for subcutaneous infusion (LCSC) (ABBV-951; Abbvie, Chicago, IL). In a clinical trial (NCT03374917), pharmacokinetics of LCSC were similar to LCIG when participants with advanced PD were treated with LCSC, confirming results seen when LCSC was given to healthy volunteers. Steady-state levels of LCSC were achieved by 2 hours, suggesting rapid conversion of prodrug to levodopa. Stable exposures of levodopa were maintained over 72 hours. A phase 3 safety study is underway (NCT03781167).

Michael Gold, MD, vice president, neuroscience development at AbbVie said, “we are most interested in areas where we can have the greatest positive effect, primarily with disease-modifying treatment, but also by taking advantage of discoveries such as Duopa, which treats the motor fluctuations that come with prolonged treatment of PD. We’ve seen that this can be life-changing for individuals with PD, and we hope to provide that to even more people with the potential subcutaneous levodopa-carbidopa infusion of ABBV-951 if approved by the FDA.”