Important Attributes of On-Demand Therapies for Parkinson’s Disease


Key opinion leaders explain the important attributes to consider when choosing an on-demand therapy.

Stuart Isaacson, MD: What are some of the important attributes of on-demand therapy, thinking about this variability of gut absorption. What do you look for?

Daniel E. Kremens, MD, JD: We want to have medications that bypass the gut so that we don’t run into those problems. We want something that works rapidly. You don’t want to remain in that OFF state for a long time because it’s incredibly uncomfortable for patients; they hate it. We want something reliable. We want to know that it’s going to break the OFF and do it reliably. We want something robust. Levodopa is thought to be the most robust medication for Parkinson disease, but apomorphine is quite robust in its ability to resemble levodopa in terms of response under the Unified Parkinson’s Disease Rating Scale.

Another thing that’s really important is that it’s convenient. It has to be a medication that the patient can use when they’re in an OFF-state and administered. Those are the things that are the main characteristics when we’re talking about on-demand therapies.

Stuart Isaacson, MD: This oral medication route is a difficult problem. We’ve recently seen pharmacokinetic studies showing that whether you give oral carbidopa or levodopa in the fed state or the fasted state, the variability between doses, even in the same person, can be so diverse. What else do you look for in an nondemand therapy? You’ve had different routes of administration and different molecules. What’s important from a patient perspective, do you think?

Daniel E. Kremens, MD, JD: I like to use the term non–GI [gastrointestinal] rather than oral because we have some on-demand therapies that are administered through the mouth but still avoid the gut.

Laxman Bahroo, DO: Patients are looking for the easiest way to deliver this medication. They are paramount in their mind. “Can I deliver it to myself easily? If I can’t, can my caregiver deliver it to me easily if I’m really in a bad OFF.” That’s the front-end consideration when we have multiple therapies in this situation, where they can use and bypass the GI tract and are able to reverse these episodes.

The way I look at it is, “Well, am I managing the therapy with the severity of OFF that you’re having? How severe is the OFF? I’m trying to get my hands around how bad of an OFF it is and maybe match the therapy with it. I’m trying to look for comorbidities, and some may prevent me from going in 1 direction or another. If somebody has pulmonary comorbidities, maybe I don’t want to go to a pulmonary therapy. Maybe somebody has orthostasis, and I don’t want to go toward apomorphine. Maybe I do want to go toward a levodopa-based therapy. I have different options there.

I want to understand the patients’ sense of urgency. How rapidly does it have to kick in? Must it go from a full off to a full on in 10 minutes or should you want to see some reduction of symptoms in about 10 minutes? How urgent is it and how severe is it are very important because it’s important for us to pick the right therapy for individuals based on what they’re looking for.

While patients are interested in the ease of dosing, we also want to talk about how the ease of dosing is as important from adherence, but if we give them a therapy that doesn’t match with their comorbidities or their severity or doesn’t kick in as quickly as expected, they’ll discontinue it. They’ll simply stop using it and say it doesn’t work.

Stuart Isaacson, MD: Some patients resolve it in solution. Do you think you can achieve a quicker ON by giving higher or different doses of oral levodopa? Do you think you have to go to a non-GI formulation?

William G. Ondo, MD: You can do some minimal improvement in the rapidity to ON. When you dissolve levodopa in a slightly acrylic solution, the most common 1 is a little water with vitamin C, or using an orange juice or a fruit juice and dissolving the levodopa in that. There have been other preparations of dissolvable levodopa, but it still dissolves and is absorbed in the gut. You can have some minimal improvement, but it’s not a dramatic improvement in duration to turning ON. As long it has to get absorbed all the way into the main intestine, that’s still a long way to travel.

Stuart Isaacson, MD: Thank you all for joining me and for watching this NeurologyLive® Peer Exchange. I hope you enjoyed the content. Please subscribe to our e-newsletters to receive upcoming Peer Exchanges and other great content right in your in-box.

Transcript edited for clarity.

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