Commentary
Video
Significance of Newly Approved IPX203 for Parkinson Disease
In this opening segment, Hauser and Fernandez discussed the FDA approval of IPX203, a new long-acting levodopa formulation for Parkinson disease, highlighting its significance in improving treatment options and patient compliance.
Earlier this month, the FDA approved Amneal Pharmaceuticals’ investigational agent IPX203, an oral formulation of carbidopa/levodopa (CD/LD) extended-release capsules, as a treatment for patients with Parkinson disease (PD). Marketed as Crexont, the therapy is an oral formulation CD/LD which includes immediate-release granules as well as extended-release pellets. In its announcement, Amneal noted it expects the oral treatment to be available to patients in the United States in September 2024.
Amneal’s CD/LD ER capsule product was approved based on data from the phase 3 RISE-PD clinical trial (NCT0300788), a double-blind study published in JAMA Neurology in August 2023. In the study, those treated with IPX203 at least 3 times per day (n = 256) showed a statistically significant improvement of 0.53 hours (95% CI, 0.09-0.97; P = .02) in daily good ON time relative to those on IR CD/LD (n = 250), who were dosed 5 times per day.
Following the approval, NeurologyLive® assembled a panel of movement disorder experts to discuss the downstream impacts of IPX203 as a new treatment for patients with PD. The panelists include Robert Hauser, MD, a professor of neurology at the University of South Florida and director of the Parkinson’s Disease and Movement Disorder Center, and Hubert Fernandez, MD, a neurologist and director of the Center for Neurological Restoration at the Cleveland Clinic.
In this segment, the duo discuss the significance of the approval and what IPX203 brings to the PD community. They touched upon the practicality of this medication and how it may simplify the treatment course for this extremely heterogeneous disease. Furthermore, the panel highlights how this agent may differ from traditional levodopa-based medications for PD.
Transcript was edited for clarity.
Robert Hauser, MD, MBA: Hi everyone, I'm Dr. Robert Hauser, Professor of Neurology at the University of South Florida, and Director of the Parkinson's Disease and Movement Disorder Center.
Hubert Fernandez, MD: And hello everyone, I am Dr. Hubert Fernandez, a neurologist, and also Professor of Neurology at the Cleveland Clinic, Lerner College of Medicine, based here in Cleveland, Ohio. I direct the Center for Neurological Restoration, where the Movement Disorders Program is housed.
Robert Hauser, MD, MBA: Yeah, so we're here this morning because we just got news that IPX203, brand name Crexont, was approved by the FDA yesterday. So Hubert, what would you say is the significance of this approval? What does it mean for clinicians and patients?
Hubert Fernandez, MD: I think the significance here really is more treatment options for what is likely still the most bothersome symptom or feature for Parkinson's patients. As you know, there isn't a one-size-fits-all approach in Parkinson's disease. It's a complex illness, so the more options we have for our patients, the better we can cater to what bothers them most.
Robert Hauser, MD, MBA: Yeah, exactly. So IPX203 is a longer-acting levodopa formulation, and levodopa is the most effective medication to treat the motor signs of Parkinson's disease. We commonly use immediate-release carbidopa/levodopa for treating these motor signs. Early on, we can give immediate-release three times a day, and it lasts from dose to dose. But over time, patients find that the immediate-release starts lasting shorter amounts of time. So it might last a couple of hours and then wear off, and those motor signs come back. They experience slowness, stiffness, tremor, and immobility during those periods we call off-time. Well, we can do a couple of things: we can move the immediate-release doses closer together, or we can add on medications, but over time, it becomes really difficult to maintain a good benefit throughout the day. So, we're looking for additional treatments, including long-acting levodopa medications, yeah.
Hubert Fernandez, MD: And then the other thing I would just add, Dr. Hauser, is the practicality of a medication that starts off with a three-times-a-day dosing in someone who is already fluctuating significantly. The conventional wisdom is that Parkinson's patients are a compliant population, so if we tell them they need to take it six, seven, or even eight times a day, most of them will do it. But some will not, and even for those who do, it can be a hardship. Simplifying the regimen while increasing the duration of on-time—or the good period of the day—is, I think, a big win for a lot of patients.
Robert Hauser, MD, MBA: Yeah, with IR, we tend to go from three times a day to four times a day, or maybe we add an additional medication, and things go okay. But after that, things get very difficult. As you mentioned, compliance becomes more challenging, and even if patients are compliant, we still face issues with protein absorption. Patients just begin to accumulate more off-time and more troublesome dyskinesia. So again, we need medications that keep patients in that good zone, which we call "good on," meaning on-time without troublesome dyskinesia throughout the day.
