MDS Poster Highlights Long-Term Sustained Efficacy of Adjunctive Continuous Subcutaneous Apomorphine Infusion

Peter LeWitt, MD

Newly presented data from the open-label InfusON study (NCT02339064) further demonstrated the long-term safety, tolerability and efficacy of adjunctive continuous subcutaneous apomorphine infusion (CSAI). All told, patients with Parkinson disease (PD) saw sustained decreases in daily OFF time and increases in good ON time over the 3-year treatment observation period, as well as perceived lower PD treatment burden and greater confidence when engaging in everyday activities.¹

These data were showcased in 2 posters presented at the 2024 International Congress of Parkinson’s Disease and Movement Disorders (MDS), held September 27-October 1, in Philadelphia, Pennsylvania. InfusON was a phase 3 study that included 99 patients with PD who experienced at least 3 hours of daily OFF time despite optimized levodopa and who had current or prior use of at least 1 additional therapy. In the trial, CSAI was initiated with a 1-2 mg bolus followed by 1 mg/h infusion, titrated to optimal efficacy and tolerability, after which participants entered a 52-week maintenance period.

Using a June 15, 2023 cutoff date, 69 of the 99 participants completed week 12, considered the primary efficacy time point, and 48 completed maintenance week 52. By week 12, results showed that the mean daily OFF time had decreased by –3.0 (SD, 3.2) h from a baseline of 6.6 (SD, 2.4) h. Although the study only had 27 patients who completed 2 years of treatment and 21 who completed at least 3, results showed that the effects on OFF time were sustained at year 1 (–3.2 [SD, 3.2] h), year 2 (–2.9 [SD, 3.2] h) and year 3 (–3.8 [SD, 4.3] h) visits.

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Led by Peter LeWitt, MD, program director of the Movement Disorders Fellowship at Henry Ford Health, the corresponding week 12 increase in good ON time was 3.1 (SD, 3.4) h from a baseline of 9.3 (SD, 2.6) h. This was sustained through the 1-year (3.7 [SD, 3.3] h), 2-year (3.2 [SD, 3.4] h) and 3-year (3.7 [SD, 3.6] h) time points. On Patient Global Impression of Change, 90%, 90%, and 86% of patients rated themselves as improved at 1, 2, and 3 years, respectively.

In the InfusON trial extension, a moderator-guided survey was conducted between January and March 2020 to evaluate treatment effect on participants’ perception of their confidence when engaging in daily activities and interpersonal relationships while using CSAI therapy. This included asking questions about confidence during physical, social, occupational, and personal care activities, as well as their ability to drive, perform work activities, household chores, and function independently without reliance on family or care partners. Among the 99 participants, 23 remained in the study at the time of the survey, and 19 (82.6%) were available and consented to be interviewed.²

Despite disease progression and CSAI being used as an add-on therapy, fewer participants (47.4%) rated their PD medication regimen (including CSAI) to be moderately, very, or extremely burdensome compared with their PD medication regimen before CSAI initiation (78.9%). The participants, who completed the 52-week maintenance period and were continuing CSAI during the extension, perceived themselves as more confident in their ability to engage in the assessed activities during CSAI treatment as compared with prior to CSAI use. The analysis was limited by the fact that it did not include individuals who dropped out prior to the time of survey conduct.

Earlier this year, at the 3rd Annual Advanced Therapeutics in Movement and Related Disorders (ATMRD) Congress, investigators presented responder rate data from InfusON, with results further demonstrated the efficacy of CSAI. At the CSAl initiation dose, authors reported that reduction in OFF time was noted, with 27% meeting response criteria prior to the first titration visit. Notably, responder rates continued to improve with CSAI optimization, reaching 61% by the start of the maintenance period and sustained through 52 weeks of the maintenance period.³

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REFERENCES
1. LeWitt P, Isaacson S, Espay A, et al. Continuous subcutaneous apomorphine infusion for Parkinson disease motor fluctuations: long-term data from the ongoing InfusON extension study. Presented at: 2024 MDS Congress; September 27-October 1; Philadelphia, PA. ABSTRACT 756
2. Agarwal P, Formella A, Crouse N, Breiteneicher A, Grall M. Continuous Subcutaneous Apomorphine Infusion (CSAI) Improved Confidence When Engaging in Everyday Activities: Survey of InfusON Study Participants. Presented at: 2024 MDS Congress; September 27-October 1; Philadelphia, PA. ABSTRACT 695
3. Isaacson SH; Ceresoli-Borroni G, Espay AJ, et al. Continuous Subcutaneous Apomorphine Infusion (CSAI) Responder Rates During Titration: Observations from the Open-label Phase 3 InfusON Trial. Presented at: ATMRD; June 22-25, 2024; Washington, DC.