Continuous levodopa/carbidopa infusion shows favourable safety and efficacy

The 3-year results of the phase 2 BeyoND trial, showed that continuous levodopa/carbidopa infusion (ND0612) had a favourable safety profile and was well-tolerated over the long term in patients with Parkinson's disease (PD) who have motor fluctuations. Participants achieved clinically relevant increases in ON-time without troublesome dyskinesia, and a decrease in OFF-time.

The 3-year results of the BeyoND study (NCT02726386) were presented by Dr Aaron Ellenbogen (Michigan Institute for Neurological Disorders, MI, USA) [1]. This open-label, phase 2 study evaluated the long-term safety of ND0612 in participants with PD who experienced ≥2 hours of daily OFF-time. The results confirmed the previously published positive outcomes after 1 year, comprising data from 214 participants, 120 of whom completed 1 year, and 114 participants entered the extension study [2]. Dr Ellenbogen highlighted that 94 participants (82.5%) completed ≥2 years and 76 (80.1%) completed ≥3 years of ND0612 treatment; some participants were already in their 7^th year. Of the 20 discontinuing participants, 10 withdrew consent and 4 experienced intolerable side effects (AEs).

At baseline, participants who entered the extension phase had a mean (± SD) OFF-time of 5.6 (± 2.9) hours and a mean Unified Parkinson’s Disease Rating Scale (UPDRS) motor score of 26.1 (±12.8). Further, 57 (50%) participants presented with a modified Hoehn and Yahr Scale score of 2, as opposed to 27 (23.7%) participants with a score of 2.5 and 30 (26.3%) participants with a score of 3. Dr Ellenbogen said the systemic safety profile was comparable with the expected profiles for a levodopa/carbidopa product. In year 1 of the extension period, 73.7% of the 114 participants showed drug-related AEs. In year 2, this percentage dropped to 36.9% of 111 participants and 39.4% of 94 participants in year 3. Infusion site reactions were common, mostly mild, and rarely led to discontinuation. These reactions also decreased over time (60.5% of participants in year 1, 26.1% in year 2, and 27.7% in year 3). The incidence of infusion-site infection shifted from 19.3% in year 1 to 9.9% in year 2, and 11.7% in year 3. Dyskinesia was seen in 3.5% of participants in year 1, none in year 2, and 1.1% in year 3.

Exploratory efficacy results in 45 participants at month 36 showed a mean reduction in OFF-time of -2.81 hours. The increase in Good ON-time was 2.79 hours.

1. Ellenbogen AL, et al. Safety and efficacy of continuous subcutaneous levodopa/carbidopa infusion for Parkinson's disease. Three-year data from the open-label BeyoND study. PL4.003, AAN 2023 Annual Meeting, 22–27 April, Boston, USA.
2. Poewe W, et al. Mov Disord. 2021;36(11):2687–92.

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Posted on 26 June, 202328 March, 2024