Continuous Subcutaneous Apomorphine Infusion Demonstrates Durable Effect on OFF, ON Time in Parkinson Disease


More than a 40% improvement in ON time without troublesome dyskinesia occurred as patients had their treatment titrated.

Stuart Isaacson, MD, director for the Parkinson’s Disease and Movement Disorders Center of Boca Raton in Florida

Stuart Isaacson, MD

Data from the open-label extension of the phase 3 InfusON trial (NCT02339064) assessing apomorphine subcutaneous infusion (CSAI) in patients with Parkinson disease (PD) motor fluctuations showed improvements in good ON and OFF time at the first titration visit, with durable effects seen 1 year into the maintenance phase.

Led by Stuart Isaacson, MD, director for the Parkinson’s Disease and Movement Disorders Center of Boca Raton in Florida, 99 patients with PD with inadequate motor control were titrated to individualized apomorphine dose to reach best waking day efficacy without intolerable adverse events (AEs). Once the optimal infusion dose was identified, patients entered a 52-week open-label maintenance period, with primary end point of change from baseline to week 12 in daily OFF time.

Presented at 2023 International Congress of Parkinson’s Disease and Movement Disorders (MDS), held August 27-31, in Copenhagen, Denmark, 85 of the original cohort completed titration. CSAI was initiated with a 1-2 mg bolus followed by a 1 mg (0.2 mL)/h infusion, with adjustments made in 0.5 to 1 mg/h increments over the subsequent 3-5 visits. Patients had infusion rates adjusted based on clinical response and tolerability, up to a maximum 8 mg/h and up to 3 daily bolus doses, with total dose not to exceed 150 mg/day.

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Overall, the median time to complete CSAI titration was 30 days. After patients began treatment, investigators recorded OFF time reductions of –0.9 h/day (n = 82) by the first titration visit and –1.7 h/day (n = 92) by the second visit. By the end of titration, mean daily OFF time was reduced by –2.8 h/day, or 39% (n = 80), compared with the 6.6 h/day (n = 94) coming into the study. In addition, treated patients demonstrated an improvement of 0.7 h/day in ON time without troublesome dyskinesia, which reached 3.0 h/day by the end of titration (43% increase).

In terms of safety, infusion site nodules was the most common treatment-related AE (63.6%), followed by dyskinesia (29.3%), nausea (24.2%), infusion site erythema (22.2%), dizziness (18.2%), and somnolence (17.2%). Titration was well-tolerated, as 86% of patients successfully entered the maintenance phase; however, 17 patients (17.2%) discontinued, mainly for infusion site nodules (4%) and nausea (3%).

The first prospective, randomized, placebo-controlled trial to assess the efficacy and safety of apomorphine infusion in patients with PD was the TOLEDO study (NCT02006121). Data from the open-label phase of the trial, published in 2021, continued to showcase the efficacy and safety of the therapy as a long-term option for persistent motor fluctuations. Pooled data from week 64 (n = 55) showed a mean change of –3.66 (SD, 2.72) hours in daily OFF time and increase of 3.31 (SD, 3.12) hours in ON time without troublesome dyskinesia.

Apomorphine infusion therapy was also found to allow substantial reductions in oral PD medication. Investigators from that trial concluded that apomorphine infusion represents a minimally invasive and easily reversible treatment option in comparison with intrajejunal levodopa/carbidopa gel and deep brain stimulation.2

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1. Isaacson S, Ceresoli-Borroni G, Espay A, et al. Early onset of efficacy during titration in US phase 3 open-label InfusON trial of apomorphine subcutaneous infusion for Parkinson’s disease motor fluctuations. Presented at: 2023 MDS Congress; August 27-31; Copenhagen, Denmark. Abstract 68.
2. Katzenschlager R, Poewe W, Rascol O, et al. Long-term safety and efficacy of apomorphine infusion in Parkinson’s disease patients with persistent motor fluctuations: results of the open-label phase of the TOLEDO study. Parkinsonism & Relat Disord. 2021;83:79-85. doi:10.1016/j.parkreldis.2020.12.024
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