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Foslevodopa/Foscarbidopa Subcutaneous Infusion Safety and Efficacy in Patients with and Without Prior Deep Brain Stimulation

Year: 2026

Type: article

Abstract: As Parkinson’s disease (PD) advances, limitations of oral medication include pill burden, increasing “Off” time, and “On” time with bothersome dyskinesia. Deep brain stimulation (DBS) can improve motor complications, but disease progression may warrant further intervention later. An approved nonsurgical option, continuous subcutaneous infusion of foslevodopa/foscarbidopa (LDp/CDp), has been shown to improve motor fluctuations, though the impact of prior DBS on its efficacy and safety is unknown. Post hoc analysis of a 52-week open-label phase 3 trial (NCT03781167) evaluated baseline characteristics, safety, and efficacy in patients treated with LDp/CDp with or without prior DBS. Fisher’s exact test, t test, Wilcoxon rank-sum test, and analysis of covariance were performed. Twenty-four (9.8%) of 244 patients received prior DBS. Both groups had similar baseline characteristics, although prior patients treated with DBS had significantly more time since diagnosis and more “speech” and “gait” impairment (Movement Disorders Society-Unified Parkinson’s Disease Rating Scale [MDS-UPDRS] Parts II/III single items). Both groups showed significant within-group improvements in “Off” time and “On” time without dyskinesia, and the between-group difference for these improvements was not significant, indicating LDp/CDp had efficacy regardless of DBS exposure. The no DBS group had significant improvement in sleep and quality of life, while the prior DBS group had nonsignificant trends in the same direction. The no DBS group had significant improvement in MDS-UPDRS Part II score but worsening in Part III score, as expected with advancing disease; change from baseline in the prior DBS group was not significant. The safety data were similar in both groups, with the only significant difference being a higher percentage of prior patients treated with DBS experiencing severe treatment-emergent adverse events than no DBS (45.8% vs 23.6%). While limited by small prior DBS patient numbers, this post hoc study suggests generally similar overall baseline, safety, and efficacy profiles in LDp/CDp-treated prior DBS and no DBS. ClinicalTrials.gov identifier NCT03781167. Parkinson’s disease (PD) is a progressive movement disorder, and the primary treatment is orally administered levodopa. However, as PD advances, oral administration of levodopa can cause unwanted and unpredictable movements called motor fluctuations and dyskinesia. Surgical deep brain stimulation (DBS) can help, but not all patients can have or want to have brain surgery, and those who do may need further intervention with disease progression. A new nonsurgical treatment continuously delivers the drug foslevodopa/foscarbidopa (LDp/CDp) under the skin 24 h a day. While LDp/CDp improves movement symptoms, it is unknown how it affects patients previously treated with DBS. We analyzed a 52-week study of LDp/CDp in patients with advanced PD, comparing 24 patients who had received DBS to 220 patients who had not. Both groups were similar before starting LDp/CDp treatment, although prior patients treated with DBS had PD for longer and had more difficulty with speech and walking. Overall, the safety measures were similar across both groups, with the only significant difference being a higher proportion of prior patients treated with DBS experiencing severe adverse events. Both groups showed significant improvements in motor fluctuations and dyskinesia. Patients who had not received DBS also showed improvements in sleep and quality of life, whereas prior patients treated with DBS did not change significantly. Motor symptoms worsened in both groups over the 52-week follow-up. Despite the limitation of a small number of previous patients treated with DBS, this study suggests that LDp/CDp is generally safe and provides movement symptom benefits in people with advanced PD, regardless of whether they had prior DBS surgery.

Source: Advances in Therapy

DOI: 10.1007/s12325-026-03579-3