Practical Considerations in the Management of OFF-Episodes in Parkinson Disease - Episode 8
Key opinion leaders in movement disorders evaluate the potential benefits and effect of an apomorphine infusion currently in development for the management of OFF episodes in Parkinson disease.
Laxman Bahroo, DO: It’s important to think about what’s also in development, where we talked about subcutaneous injectable as a rescue and as a bridge, we talked about the sublingual as a bridge for this, and then there’s challenges with either or but there’s apomorphine infusion in development. And this of course is a subcutaneous injectable. But it’s not a bridge or rescue. This would be maintenance because of how it’s delivered. It’s going to be delivered through a pump and dosed over a 16-hour period. This would flip the algorithm of medications on their head in some way. We’ve always thought of apomorphine for years, whether you’ve used injectable or just only the sublingual and are now looking at injectable as rescue/bridge medications. But here it would be a maintenance medication, a nonsurgical infusion option, where we could utilize this to be able to manage OFFs. And the most important thing I think about its development is it’s a non-GI [gastrointestinal]-based option. For all our non-GI-based options, as we talked about all 3 of the on-demand therapy share 1 characteristic, they’re absorbed orally in the lungs, or subcutaneously, but they’re all first short acting episodes here. We’re going to come on out with a non-GI-based option for maintenance. And if you think about all our medications, we don’t have a single non-GI-based option for our meds, except for the transdermal. But in advancing Parkinson’s is an adjunctive medication. Whereas this would become, this is a much more potent dopamine agonist effect. It’s the most potent dopamine agonist. And I’m interested in seeing how this develops and if it’s approved. It would be an option for my patients that are fluctuating on their current regimen, and we’ve added adjuncts and we’ve added on-demand therapy, or despite that they can’t tolerate any more adjuncts. And they’re kind of still fluctuating in that sense, both dyskinesia and OFFs, and this may be an option to consider using the medication to be able to reduce these OFFs and to fine tune where the oral medications are a little longer providing them the relief that they once did.
Sanjay Iyer, MD: I see the apomorphine infusion as a game-changer seeing the data from the UK [United Kingdom] and the EU [European Union] and what patients have experienced haven’t been quite as excited about any product in several years. You think how many people may be able to avoid surgery, avoid DBS[deep brain stimulation], they’re the folks who require frequent levodopa. They’re getting a lot of dyskinesia. If we could put them on the apomorphine infusion, deliver a steady dose all through the day, and obviously, as a dopamine agonist will have less potential for dyskinesia and how much can you reduce to levodopa. It’s going to be a game-changer. And a lot of my patients who have been reading about it are very excited to hear that it’s coming.
Laxman Bahroo, DO: Absolutely. And this was my conversation today with this lady who came in and said I’m on an extended-release levodopa, we’ve adjusted the dosing. And about 3, 4 months ago, she transitioned to adding subcutaneous apomorphine and, well, it works. And she came to my clinic in an OFF-state and her husband injected her in front of me and I immediately put a timer on. And as I put a timer on, I said, “Let’s see what happens.” At about 9 minutes, she went from an OFF where she was having a lot of freezing of gait, difficulty walking, difficulty turning, to being able to get up and walk down a hallway much more easily. And then about 5 or 6 minutes later, the husband said, “What do you think she’s on?” Now I said, she should be even further along. She got up and did the same thing. And we all said, “OK, now you know how this works.” And I said, “You’re fluctuating even with these combinations.” I introduced this topic of this may be an infusible option for you. And I said, when it comes into development, if it comes into development, this may be an option for us to consider utilizing. And I think, would you need a caregiver for this? In some cases, yes. Depending on the functioning of the person, you may need a caregiver for this, but the most appealing thing is it’s nonsurgical. And if you look at how much our adjunct medications give, if you look at any adjective medications, we hit about a 2-hour limit with an adjunct. Under 2 hours or under. Some give 1 hour, 1.5 hours, but every adjunct adds about 2. If you look at the TOLEDO study, which was like everybody on a combination of medications, what I would call a moderate advancing population of Parkinson’s and the added placebo or the added apomorphine infusion, you’ll see in reduction that’s higher than the typical things. Things we see with surgical therapies, DBS
With carbidopa/levodopa enteral solutions, we see that because it’s a surgical therapy. You see it with DBS but you’re seeing a similar reduction, a more robust reduction to the typical adjunct of therapies. And Dr Iyer, you said it, this is a therapy you’ve been excited about because it’s a therapy that’s different in some ways, because of all the different options we talked about. And while it has an interesting mechanism of action, but that mode delivery makes it a very interesting option.
Sanjay Iyer, MD: After a number of years of having Parkinson’s and being on carbidopa/levodopa, many of my patients tell me, “I don’t really feel like I’m ON anymore.” And no matter how much more we give them, maybe it’s GI issues, maybe it’s other things, they just don’t feel they’re ON. And some of these folks I’m putting them on the injectable subcutaneous apomorphine to see do they get a response? And those are the folks that I’m just telling you, this is so exciting because when the pump is available, we’re going to be able to turn you ON. And they’re very excited about it.
Laxman Bahroo, DO: On a side note of this and to talk about this in terms of patients, I have individuals on CLES [carbidopa/levodopa enteral suspension], the enteral solution formulation of levodopa. And even with that, at times, they will use apomorphine subcutaneous injections because they wake up first thing in the morning and they’re OFF because again, that’s a 16-hour option and they wake up in an OFF state, or they have nocturnal OFFs and despite taking oral medications at night. They’ll use subcutaneous apomorphine either overnight or first thing in the morning or both. And of course, the pump is not compatible with water, if they shower or if they go swimming, they will use the apomorphine subcutaneous injectable to be able to bridge themselves from the turning OFF the pump to turning on the pump or in that portion. This is not a mutually exclusive option, but this is an option that they can utilize to bridge themselves with those gaps.
Transcript Edited for Clarity