Reduction in Parkinson OFF Episodes Through Subcutaneous Apomorphine Infusion Leads to Doubling of Good ON Time

A post-hoc analysis of patient diary data from the phase 3 InfusON trial (NCT02339064) showed that treatment with continuous subcutaneous apomorphine infusion (CSAI; Onapgo; Supernus Pharmaceuticals) led to a significant reduction of daily OFF episodes in patients with Parkinson disease (PD), which more than doubled the amount of uninterrupted good ON time each day.¹

In the 12-week study, patients on CSAI demonstrated an average total daily good ON time increase of 42%, and total daily OFF time decrease by 39%. From baseline to week 12, the longest duration of uninterrupted good ON time went from 4.4 hours to 9.6 hours (n = 65). In addition, the total daily duration good ON time went from 9.3 hours to 12 hours, while the totally daily duration of OFF time decreased from 6.6 hours to 3.5 hours.

Presented at the 2025 Advanced Therapeutics in Movement and Related Disorders (ATMRD) Congress, held June 27-30 in Washington, D.C., the post-hoc analysis mapped 24 hours of diary recordings, with wake-up time set as the first of 4 consecutive awake intervals beginning no earlier than 3:00AM. Of the 99 participants treated in the phase 3 trial, 65 (65.7%) had evaluable diaries for heat map analysis at both baseline and maintenance period week 12.

Led by Daniel Kremens, MD, JD, co-director of the Parkinson’s Disease and Movement Disorders Center at Thomas Jefferson University, patients come into the study with a mean age of 61.6 (±9.41) years, coupled with a mean OFF time of 6.6 (±2.36) hours. All patients were on levodopa products, while a majority were on dopamine agonists (79.8%) and less on MAO-B inhibitors (33.3%), COMT inhibitors (20.2%), and amantadine (31.3%). Entering the trial, participants had a mean duration of 5.3 (±4.33) years of motor fluctuations.

By week 12 of treatment, the average number of OFF episodes reduced from 4.5 to 2.8 episodes per day. Coming into the study, participants had an average ON time without troublesome dyskinesia of 9.3 (±2.62) hours and an ON time with troublesome dyskinesia of 0.5 (±1.03) hours. Despite dyskinesia being a commonly reported adverse event (AE), fewer participants reported any troublesome dyskinesia at week 12 (n = 6) than at baseline (n = 12).

In the post-hoc analysis, almost all participants self-reported improved health status at week 12. Of these, 55.4% reported much improved, 21.5% were minimally improved, and 20.0% rated themselves as very much improved. Overall, improvement was meaningful to participants with all but 2 (97%) reporting improvement; 75% reported either being much improved or very much improved.

READ MORE: Subcutaneous Foslevodopa/Foscarbidopa Enhances Sleep and QoL Synergistically in Parkinson Disease

In terms of safety, as noted, the most common AEs observed were infusion site nodules, dyskinesia, and nausea, which occurred more often during titration. Despite the prevalence of dyskinesia, diary data showed that, overall, dyskinesia decreased throughout the 12-week study. Notably, 33.3% of patients discontinued because of an AE; however, infusion site nodules, typically mild to moderate in severity, were not the main cause of discontinuation.

The open-label extension of InfusON, presented at the 2023 International Parkinson and Movement Disorders Society Congress (MDS), further demonstrated CSAI’s impact on patients with PD. Following titration, patients on the therapy 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 had 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).²

The TOLEDO study (NCT02006121) was the first prospective, randomized, placebo-controlled trial to evaluate the efficacy and safety of apomorphine infusion in patients with PD. Findings from its open-label extension, published in 2021, reinforced the therapy’s long-term benefits for managing persistent motor fluctuations. By week 64, pooled data from 55 patients showed a mean reduction of 3.66 hours in daily OFF time and an increase of 3.31 hours in ON time without troublesome dyskinesia.³

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REFERENCES
1. Kremens D, Hauser RA, Formella AE, Joshi M, Grall M. Improvement in Uninterrupted good ON time and reduction in OFF periods with CSAI treatment. Presented at: 2025 ATMRD Congress; June 27-30. Minneapolis, MN.
2. 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.
3. 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