Efficacy and Safety of Foslevodopa/Foscarbidopa Monotherapy in Patients with Parkinson's Disease

Abstract

Background: As Parkinson's disease (PD) progresses, managing symptoms becomes increasingly difficult. Foslevodopa/foscarbidopa (LDp/CDp), a 24-hour/day continuous subcutaneous infusion of levodopa/carbidopa (LD/CD) prodrugs, improves motor complications. The feasibility and sustainability of LDp/CDp monotherapy warrants investigation.

Objective: The aim was to report the efficacy and safety of LDp/CDp monotherapy and combination therapy.

Methods: This post hoc analysis assessed patients with PD and ≥2.5 "Off" hours/day receiving LDp/CDp monotherapy or combination therapy in 3 trials: a 12-week randomized active-controlled trial (RCT) comparing LDp/CDp with oral immediate-release LD/CD (NCT04380142), a 52-week open-label trial of LDp/CDp (NCT03781167), and its 96-week open-label extension study (OLE; NCT04379050). Monotherapy was defined as receiving LDp/CDp without concomitant PD medications; combination therapy was defined as receiving LDp/CDp with other PD medications.

Results: In the RCT, 74 of 141 patients received LDp/CDp. The 52-week trial enrolled 244 patients; 129 entered the OLE. Of LDp/CDp-treated patients, 19 of 74 (25.7%) in the RCT, 49 of 244 (20.1%) in the 52-week trial, and 46 of 129 (35.7%) in the OLE received monotherapy. In the RCT, mean (standard deviation) change from baseline to week 12 in "Off" time was -4.5 (4.4) and -3.0 (3.5) hours for monotherapy and combination therapy, respectively; +4.1 (3.7) and +3.1 (3.6) hours for "On" time without troublesome dyskinesia; and +4.0 (3.6) and +4.0 (3.9) hours for "On" time without dyskinesia. Efficacy was similar in open-label trials. Improvements in the Movement Disorder Society-Unified Parkinson's Disease Rating Scale Part II, 39-item Parkinson's Disease Questionnaire, Parkinson's Disease Sleep Scale-2 scores, and overall safety were comparable between monotherapy and combination therapy groups.

Conclusions: LDp/CDp monotherapy treatment may be suitable for up to 96 weeks.

Keywords: Parkinson's disease; foslevodopa/foscarbidopa; monotherapy; subcutaneous infusion.

FIG. 1

LDp/CDp monotherapy sustained throughout the (A) 12‐week RCT, (B) 52‐week trial, and (C) 96‐week OLE. LDp/CDp, foslevodopa/foscarbidopa; OLE, open‐label extension; RCT, randomized active‐controlled trial.

FIG. 2

Change from baseline to final visit in (A) “Off” time, (B) “On” time without troublesome dyskinesia, and (C) “On” time without dyskinesia. Reported values are mean (SD [standard deviation]) change from baseline to week 12 for the RCT and mean (SD) change from baseline to final available visit for the 52‐week trial and 96‐week OLE. The baseline of the 96‐week OLE corresponds to the start of the 52‐week trial. *P ≤ 0.05, **P ≤ 0.01, and ***P ≤ 0.001 versus baseline. BL, baseline; Combo, combination therapy; LD/CD, levodopa/carbidopa; LDp/CDp, foslevodopa/foscarbidopa; Mono, monotherapy; OLE, open‐label extension; RCT, randomized active‐controlled trial.

FIG. 3

Change from baseline to final visit in (A) MDS‐UPDRS Part II score, (B) PDQ‐39 summary index total score, and (C) PDSS‐2 total score.^a Reported values are mean (SD [standard deviation]) change from baseline to final available visit except for MDS‐UPDRS Part II data for the 12‐week RCT, which is change from baseline to week 12. Baseline of the 96‐week trial corresponds to the start of the 52‐week trial. *P ≤ 0.05, **P ≤ 0.01, and ***P ≤ 0.001 versus baseline. BL, baseline; Combo, combination therapy; LD/CD, levodopa/carbidopa; LDp/CDp, foslevodopa/foscarbidopa; MDS‐UPDRS, Movement Disorder Society‐Unified Parkinson's Disease Rating Scale; Mono, monotherapy; OLE, open‐label extension; PDQ‐39, 39‐item Parkinson's Disease Questionnaire; PDSS‐2, Parkinson's Disease Sleep Scale‐2; RCT, randomized active‐controlled trial. ^aPDSS‐2 was not evaluated in the OLE.

FIG. 4

LDp/CDp treatment patterns for patients who completed the 52‐week parent trial and enrolled in the 96‐week open‐label extension. LDp/CDp, foslevodopa/foscarbidopa; OLE, open‐label extension. ^aAt baseline of the OLE study, data were missing for 2 patients receiving monotherapy. ^bAt OLE study week 72, data were missing for 2 patients receiving combination therapy and 1 patient receiving monotherapy; 1 patient at weeks 24 and 48 of the OLE study had switched from monotherapy to combination therapy, but at week 72, 0 patients with available data had switched from monotherapy to polytherapy.