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Considerations for the Maintenance of ON Time in Parkinson Disease - Episode 16

Novel Therapeutic Administration Routes for Managing PD OFF Episodes

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Robert A. Hauser, MD, MBA, and Rajesh Pahwa, MD, highlight novel administration routes for the management of OFF episodes in patients with Parkinson disease.

Stuart Isaacson, MD: Let’s talk about that gap. You bring up an interesting vista to the future directions in managing OFF episodes. Bob, you’ve been involved in a lot of programs. You’ve mentioned earlier if that we could have a twice-a-day oral, or we could have a transdermal that was robust and well tolerated. There’s continuous infusions being looked at. Where do you think this is heading? Do you think we need a novel administration route or a fancy long-acting oral medication? What do you think the routes are if the patients have gone through a lot of these classes of medications, as Raj has described? We have on-demand therapies, but we need to make sure they’re doing it right. They don’t want to go for surgical therapies, whether it’s in the skull or in the abdomen. Where do you think this is heading?

Robert A. Hauser, MD, MBA: There are going to be continued efforts to come up with a very long-acting oral carbidopa-levodopa formulation. There’s a longer acting carbidopa-levodopa formulation in development called IPX203. Results were just made public for that, so that looks encouraging. It’s certainly not a once- or twice-a-day therapy. Most people might need that 3 or 4 times a day, but there are going to be ongoing efforts to figure out how can we get closer to a twice-a-day oral. That seems very appealing to me. That’s the way most medications are given. If a manufacturer could come up with that, that would be ideal.

The other route that’s getting a lot of attention is subcutaneous infusion. In development there’s a subcutaneous carbidopa-levodopa infusion, plus another version of that by another manufacturer, as well as apomorphine for subcutaneous infusions. These are certainly going to hit the market. They have limitations related to a delivery system and the medications themselves. They’re going to try to, as much as possible, fill the gap between our oral medications and device-aided therapies or surgery.

Stuart Isaacson, MD: Raj, do you think these subcutaneous infusions will be additional advanced therapies? Or do you think they’re going to fill an intermediate role somewhere between the orals and the surgical options?

Rajesh Pahwa, MD: They’ll fill this gap between the intermediate and the surgical therapies with whatever we end up calling these pump therapies for it. The only thing is we can’t call them pump therapies because the carbidopa-levodopa and enteral suspension is also delivered via pump. We have patients in whom we’ve tried adjunctive therapies and who we’ve given on-demand therapies. Either they’re not ready to go for surgery, or their symptoms aren’t severe enough to require surgery, but they’re still having OFF time. Even starting levodopa subcutaneous infusion using an apomorphine subcutaneous infusion may give them enough ON time without requiring brain stimulation or carbidopa-levodopa enteral suspension, both of which require surgery to get to that therapy. This is 1 unmet need that, in the near future, we may help our patients fill. I’m very excited about this therapy, which hopefully will be available soon.

Transcript Edited for Clarity