Optimizing Parkinson Disease Care With Newly Approved Continuous Infusion Therapy

Julie Pilitsis, MD, PhD, MBA

(Credit: The University of Arizona)

Parkinson disease (PD) is characterized by progressive neurodegeneration of the substantia nigra, leading to striatal dopamine deficiency and motor symptoms. Although studies have shown the efficacy of dopamine replacement therapy, most patients eventually develop motor fluctuations that require treatment adjustment.¹ Deep brain stimulation and continuous dopaminergic drug delivery offer effective options for managing persistent motor complications, though both are invasive. Apomorphine, a potent dopamine agonist approved for severe motor fluctuations, has displayed significant reductions in "OFF" time and levodopa requirements in uncontrolled studies. However, despite its long-standing clinical use, its efficacy had previously not been validated in randomized controlled trials.

Addressing this gap, the FDA recently approved Supernus Pharmaceuticals’ investigational agent SPN-830 (Onapgo), an investigational subcutaneous apomorphine infusion device, for the treatment of motor fluctuations in adults with advanced PD.¹ The therapy’s approval was based on data from the TOLEDO study (NCT02006121), a randomized, double-blind study in which treatment with the device was associated with a difference of –1.89 hours per day of OFF time for patients with PD in comparison with placebo. Published in the Lancet Neurology in 2018, the study randomly assigned 106 patients living with the disease to either 3-mg/hour to 8-mg/hour dose of apomorphine (n = 53) or placebo saline infusion (n = 53) during their wake hours for a 12-week period.²

To explore the clinical implications of this newly approved therapy, Julie Pilitsis, MD, PhD, MBA, chair of the department of neurosurgery at the University of Arizona and the physician executive for functional neurosurgery for Banner Health, spoke with NeurologyLive® in a recent interview. She discussed the potential impact of continuous infusion therapy on the standard of care for moderate to severe PD, key considerations for clinicians when selecting between medication-based, device-based, or surgical treatments, and the importance of addressing non-motor symptoms alongside traditional motor symptom management. Pilitsis also underscored the need for a comprehensive, individualized approach to optimizing patient outcomes in PD.

NeurologyLive: So, for our clinical audience, could you share with us your immediate reaction to this approval?

Julie Pilitsis, MD, PhD, MBA: Well, thanks so much for having me. I'm excited about any therapy that's offered to patients who suffer from Parkinson. I think one of the hardest parts about Parkinson, especially as the disease progresses, is how unpredictable it is. People don't like to make plans because they're not sure what they're going to be able to do that day—their responses to medication become unreliable. They have very good days and very bad days. They have times when they are “ON” medication and able to do things, and times when they are "OFF” medication and really can't do much of anything.

So, why I'm excited about this therapy is because it reduces that "OFF" time, allowing people to improve their quality of life by maintaining stability. It enables them to commit to activities and have some predictability in their daily lives, which is really important.

How do you anticipate the introduction of this new therapy into the landscape of PD care, and do you see it having positive downstream effects later in care or even in drug development?

Yeah, so the idea here is that patients receive a constant infusion of medication, meaning they don’t have to wait for a drug to reach steady-state—it keeps them at that steady level all the time. Right now, this therapy is approved for patients with moderate to severe Parkinson, and many of these patients experience the greatest impact on their quality of life. Keeping them at a steady state, I believe, will improve their overall well-being.

It also helps balance out all the other symptoms of Parkinson. When we think about Parkinson, we often focus on the visible symptoms—tremors, slowness, stiffness—but there are many symptoms that aren’t visible, such as pain, constipation, and urinary difficulties. Being able to address both motor and non-motor symptoms is essential, and I think that will be really meaningful for patients.

There was a lot of data to support this approval. For our audience, what would you say are the most significant findings from some of the studies on this treatment?

I think one of the most troublesome aspects of Parkinson is these periods of "OFF" time. The fact that this therapy reduces those periods is significant and has a real impact on patients. Sometimes, when you see statistics, you think, "Oh, it’s this much better than placebo," but in this case, reducing "OFF" time truly makes a dramatic difference.

Of course, like with any medication, there are some adverse effects. People may experience nausea or, in some cases, a rash. Any time you have a device, there can be challenges that come with wearing it. Patients need to ensure they can tolerate these potential adverse events.

I’m excited because the previous iteration of these devices involved administering drugs through the stomach, which was a bit messy and difficult for patients to use. This new therapy is much more similar to what’s available for diabetics, making it more user-friendly. We now have extensive literature showing that this is a viable and well-tolerated option for many patients.

Is there anything else clinicians should consider when prescribing this therapy and important for the clinical community to know about this treatment?

I think whenever you’re prescribing a therapy—especially one that involves a device—it’s important for patients to take a holistic view of all their options. Is there another oral medication that might be a better fit for them? Can they tolerate it?

On the flip side, we also have very effective surgical therapies for Parkinson, such as deep brain stimulation or focused ultrasound, which can significantly improve quality of life. Is one of those a better option for the patient?

What’s important is that patients see a movement disorder neurologist to discuss all their options. That way, they can be empowered to make the best decision for their individual needs.

Transcript edited for clarity.

REFERENCES
1. Supernus Announces FDA Approval of ONAPGO™ (apomorphine hydrochloride) for Parkinson’s Disease. News Release. Supernus. Published Febrauary 4, 2025. Accessed February 4, 2025. https://ir.supernus.com/news-releases/news-release-details/supernus-announces-fda-approval-onapgotm-apomorphine
2. Katzenschlager R, Poewe W, Rascol O, et al. Apomorphine subcutaneous infusion in patients with Parkinson's disease with persistent motor fluctuations (TOLEDO): a multicentre, double-blind, randomized, placebo-controlled trial. Lancet Neurol. 2018;17(9):749-759. doi:10.1016/S1474-4422(18)30239-4