Mechanism of Action of IPX203

EP: 1.Significance of Newly Approved IPX203 for Parkinson Disease

Now Viewing

EP: 2.Mechanism of Action of IPX203

EP: 3.Phase 3 RISE-PD Trial and Supportive Evidence for IPX203

EP: 4.Safety Considerations for Newly Approved IPX203

EP: 5.Properly Integrating Newly Approved IPX203 in the Care of Parkinson Disease

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 Hauser and Fernandez provide commentary on the ins and outs of IPX203 and how it operates as a treatment for patients with PD. The clinician panel provided insight on how it differs from previously approved medications, some of the advantages it holds, and the flexibility patients get with this treatment. Furthermore, they touched upon how IPX203 utilizes an advanced delivery technology system to prolong therapeutic effects in this patient population.

Transcript below edited for clarity.

Robert Hauser, MD: Hubert, can you tell our audience, what is IPX203?

Hubert Fernandez, MD: I think my favorite part of this medication is the way it is engineered—it's the best product we know, the best treatment we know for Parkinson's as of today. So it uses levodopa medication, but also the technology, the advancement in the delivery of the medication to prolong the efficacy of levodopa. It’s a combination of immediate-release and extended-release levodopa. The way they do this is, for levodopa, a quarter of it is in immediate-release granules. And even for those granules, there's a disintegrating polymer to make the absorption faster for these immediate-release granules, and 75% of the levodopa is in extended-release beads. And within those beads, first, it's enteric-coated so that it dissolves a little slower, and then there's this mucoadhesive polymer so it sticks to the small intestines. There is a very short area in the small intestines where absorption is most optimal. And you know, as you know, the small intestines don’t think; they just keep moving whatever is digestible and absorbable down the pipeline. And so, we want it to stick a little longer so more of it is absorbed. That mucoadhesive polymer there increases the duration of absorption for the extended-release beads, and then the next layer for that is the controlled-release polymer, or the slow-release polymer, so that while it’s sticking and being absorbed, it’s absorbed slowly over time, so more of it is absorbed for a longer duration. And then you have the levodopa. Of course, 75% of it is reserved for the extended release. So the net effect is that the 25% of immediate-release granules will work quickly to provide a sooner duration of action, and then the extended-release beads, the 75% of the remaining levodopa, through creative engineering, are absorbed slowly over time to provide that longer duration. So I think it’s a neat product to have thought of all these ways to optimize absorption.

Robert Hauser, MD: Yeah, that’s right, that mucoadhesive polymer is unique to this product, and if you look at the pharmacokinetics, it can maintain levodopa levels for about six hours or so. Now, that doesn’t mean that patients will get a clinical response lasting six hours, so keep that in mind, but it does maintain those levodopa levels.