AAN 2025: Less off time, more good on time with long-term Onapgo
Benefits seen with 3 years of treatment in advanced Parkinson's patients
Treatment for up to three years with Onapgo (apomorphine hydrochloride) — approved in the U.S. earlier this year as an add-on therapy for advanced Parkinson’s disease — significantly and sustainably reduced off time, when symptoms are not fully controlled, in adults with the neurodegenerative condition.
Importantly, the researchers noted, reductions in off periods were matched by improvements in good on time, when symptoms are well controlled, among patients taking part in a clinical study.
These new results come from the extension part of the Phase 3 INFUS-ON trial (NCT02339064), which assessed the therapy’s long-term use in people with advanced Parkinson’s.
The data were presented in a poster, titled “Continuous Subcutaneous Apomorphine Infusion for Parkinson Disease Motor Fluctuations: Long-term Data from the Ongoing InfusON Extension Study,” at this year’s American Academy of Neurology (AAN) Annual Meeting, held April 5-9, in San Diego and online.
“These data support the long-term safety, tolerability, and efficacy of adjunctive [or add-on treatment],” the researchers wrote in the presentation’s abstract.
Onapgo approved in US earlier this year to reduce Parkinson’s off time
Parkinson’s is caused by the dysfunction and death of dopaminergic neurons, the nerve cells responsible for producing dopamine, which is a signaling molecule involved in motor control. Standard treatment includes levodopa, which contains a molecule cells can use to produce dopamine.
Levodopa is usually effective at controlling Parkinson’s motor symptoms. However, its long-term use is associated with off episodes, when the medication’s effects wear off between doses, as well as dyskinesia, or sudden, uncontrolled movements.
Onapgo is a formulation of apomorphine, a medication that mimics dopamine’s activity in the brain, that’s now approved in the U.S. as an adjunctive, or add-on, treatment to manage off episodes in people with advanced Parkinson’s. It is delivered as a continuous subcutaneous, or under-the-skin, infusion.
The treatment’s approval was based on data from the INFUS-ON trial, sponsored by Supernus Pharmaceuticals, the company that markets the treatment in the U.S. All of the investigators involved in the new clinical study are Supernus employees or have served as paid consultants to the pharmaceutical.
INFUS-ON was an open-label study that assessed the safety and efficacy of Onapgo in 99 adults with advanced Parkinson’s at 19 sites in the U.S. Participants had a mean age of 61.6, and a mean disease duration of 10 years. Slightly more than two-thirds (69%) were men. Overall, these patients experienced motor fluctuations for a mean of 6.6 hours per day.
Onapgo was started with a small 1-2 mg dose, followed by a steady infusion of 1 mg per hour. The dose was slowly adjusted to find the best balance between effectiveness and side effects, without taking more than 8 mg per hour or 150 mg per day. This was followed by a one year maintenance period.
Patients who completed the maintenance period could continue treatment in an ongoing extension period. Data from the maintenance period demonstrated the treatment was generally safe and well tolerated, and reduced off time while increasing good on time.
In self-reported ratings, over 85% of patients called themselves ‘improved’
At AAN, the researchers shared results from up to three years of treatment during the extension part of the trial. Among the 48 patients who completed the maintenance period, 45 continued to the extension phase. Of them, 27 completed a total of two or more years of treatment, with 22 having three or more years, through January 2024.
The results remained positive, the researchers noted.
“By week 12, mean … daily off time decreased, … and this was sustained at the [one]-year … [two]-year … and [three]-year … visits,” the researchers wrote.
Meanwhile, “corresponding week 12 increases in good on time were [seen] from … baseline [and] … also sustained at the [one]-year … [two]-year … and [three]-year … visits,” the team wrote.
Onapgo was generally safe and well tolerated over the three years of treatment, with adverse events mainly occurring during the dose adjustment period. The most common adverse events were nausea, somnolence, or daytime sleepiness, and dizziness; these symptoms were infrequent in the long term. Although nodules at the infusion site were common, they were rarely severe, and no infusion site infections occurred during this period.
The fraction of participants who rated themselves as improved compared to baseline … was 90% at [one] year, 90% at [two] years, and 86% at [three] years.
Overall, treatment reduced daily off time by more than three hours per day, an effect that persisted through three years of treatment. Alongside that decrease was the corresponding increase of more than three hours of good on time daily.
A large number of participants — more than 85% overall — consistently said they felt better compared with baseline, or when they started treatment, based on a self-assessment tool. This stayed true throughout all three years of the study, showing that the improvement was meaningful and lasting.
“The fraction of participants who rated themselves as improved compared to baseline … was 90% at [one] year, 90% at [two] years, and 86% at [three] years,” the researchers wrote.
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