Real-World EU Data Suggest Safety of High-Dose Apomorphine Infusion in Parkinson Disease | NeurologyLive

Long-term, higher-dose continuous subcutaneous apomorphine infusion (CSAI; Onapgo; Supernus Pharmaceuticals) appears to be safe and tolerable for patients with advanced Parkinson disease (PD), according to data from a real-world European-based study.¹ The treatment received FDA approval in February 2025.²

The therapy’s safety profile remained consistent with prior studies of lower-dose infusions. A total of 41.3% of patients reported at least 1 adverse event (AE), the majority of which were infusion site reactions. Skin nodules were the most frequently reported AE, occurring in 38.1% of patients (n = 24). Other reported events included hallucinations (4.8%) and hypotension (1.6%). Importantly, no reported AEs led to dose reductions or discontinuation of high-dose CSAI.

Mindy Grall, PhD, MSN, a senior director of Medical Affairs at Supernus, and colleagues presented the data in a poster at the 2025 International Congress of Parkinson’s Disease and Movement Disorders (MDS), held October 5-9, in Honolulu, Hawaii. The senior author of the effort was Marc Vérin, MD, PhD, a professor of neurology and director of the Behavior and Central Gray Nuclei Research Unit at the Université d’Orléans.

Prior clinical trials—mainly TOLEDO (NCT02006121) and InfusON (NCT02339064)—supported the recent approval of CSAI in the United States, few patients in those studies received doses of higher than 6 mg/h or 100 mg/day for extended durations. To address this evidence gap, investigators analyzed data from 72 patients in the United Kingdom, Spain, France, and the Netherlands who were prescribed CSAI at or above these dosing thresholds for at least 6 months, with 87.5% (n = 63) having received treatment for more than 1 year.

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Infusion Rate and Duration Findings

Across the cohort, 95.2% of patients used modal infusion rates of 6 mg/h or higher, with 17.5% receiving doses of at least 8 mg/h. In terms of daily exposure, 74.6% of patients had modal daily doses exceeding 100 mg, and nearly one-third (30.2%) were prescribed more than 140 mg/day.

The average duration of daily infusion at these rates was 19 hours, with a range of 12 to 24 hours. Use patterns varied: 49.2% of patients used CSAI during daytime hours only, while 50.8% continued infusion into the night, often at reduced nighttime rates.

The cohort had a mean age of 71.2 years and consisted of 67% male patients. Among the 35 patients for whom disease duration data were available, the median duration of Parkinson disease was 19 years (range, 8–47), with mean CSAI exposure at high-dose thresholds lasting approximately 1479 days (range, 195–7439).

“These real-world data suggest some [people with PD] may benefit from, and can be safely maintained on, CSAI doses ≥6mg/h or ≥100 mg/d,” Grall, Vérin, and colleagues wrote, adding that the EU-based data “extend the available safety and tolerability information about higher doses of CSAI.”

ATMRD 2025: InfusON Post-Hoc Data

Earlier this year, a post-hoc analysis of patient diary data from the phase 3 InfusON trial (NCT02339064) presented at the 2025 Advanced Therapeutics in Movement and Related Disorders (ATMRD) Congress, held June 27-30 in Washington, DC, showed that treatment with CSAI led to a significant reduction of daily OFF episodes in patients with PD, which more than doubled the amount of uninterrupted good ON time each day.³

Across the 12-week period, patients on CSAI demonstrated an average total daily good ON time increase of 42%, and total daily OFF time decrease by 39%. From baseline, 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.

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 3:00 AM. 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.

Additional Expert Insight on CSAI

Following the infusion therapy’s approval earlier this year, NeurologyLive sat down with movement disorder experts Stuart Isaacson, MD, director of the Parkinson’s disease and movement disorders center of Boca Raton, and Rajesh Pahwa, MD, the Laverne and Joyce Rider professor of neurology at the University of Kansas Medical Center to discuss the clinical potential of the new treatment in a special episode of the Mind Moments podcast.

The duo discussed the significance of the approval, considerations for patient selection with the treatment, as well as the studies supporting its safety and efficacy. In addition, the pair provided context on how this approval, along with other recent approvals in PD, speak to the progress the clinical and research community has made over the years.

You can to the full episode with Isaacson and Pahwa below:

Click here to read more from MDS 2025.

REFERENCES
1. Grall M, Parsons J, De Groot A, Sesar A, Qin P, Verin M. European experience with long-term continuous subcutaneous apomorphine infusions at higher doses. Presented at: International Congress of Parkinson’s Disease and Movement Disorders; October 5-9, 2025; Honolulu, HI.
2. Supernus Announces FDA Approval of ONAPGO™ (apomorphine hydrochloride) for Parkinson’s Disease. News Release. Supernus. Published February 4, 2025. Accessed October 5, 2025. https://ir.supernus.com/news-releases/news-release-details/supernus-announces-fda-approval-onapgotm-apomorphine
3. 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