Emerging Novel Therapies in Development for PD


Kremens gave thoughts on the use of several investigational continuous agents, including IPX203, risvodetinib, and P2B001.

At the 2024 American Academy of Neurology Annual Meeting, NeurologyLive® sat down with Parkinson disease (PD) expert Daniel Kremens, MD, JD, to discuss some of the top data being presented at the meeting on novel approaches in development for the treatment of the movement disorder. Kremens discussed these various presentations, offering his perspective on the clinical landscape.

In this segment, Kremens discussed several novel, emerging therapies in the pipeline that have shown promise in phase 2 and phase 3 studies. He first touches on a study assessing modal dose ranges for IPX203, an extended-release caribidopa-levodopa solution. In addition, he covers promising data on risvodetinib, a selective inhibitor of nonreceptor c-Abl, and P2B001, an extended release combination formulation of pramiprexole and rasagiline.

00:00 – Testing modal ranges of IPX203

01:00 – Risvodetinib and c-Abl inhibitors for PD

02:20 – Safety of combination therapy P2B001

Transcript below edited for clarity.

Daniel Kremens, MD, JD: IPX203 is not yet approved, but there has been positive data in the pivotal trial, the RISE-PD study, and its long term follow up. In a post hoc analysis of the long-term follow-up, investigators looked at different what they called modal ranges of the doses, ranging from a little over 500 milligrams of levadopa to over 5000 milligrams of levadopa. What they found in the study was that the drug could be safely used over the long term without the emergence of additional side effects even at the different modal ranges of the dosing. Even at higher doses, the drug was safe and well tolerated over extended periods of time.

Risvodetinib is a selective inhibitor of c-Abl. c-Abl is a tyrosine kinase that's implicated in the aggregation of alpha-synuclein in Parkinson disease. There have been a number of studies looking at this class of compounds, and this is the latest one. Some of the folks listening may have been familiar with nilotinib, which was an earlier c-ABL compound that in a large study was not successful. Although there were some signals that this class of medicines holds promise. Certainly in preclinical and animal models, it has been shown to be effective. What we're going to learn at this year's conference is data on the safety and efficacy of this new compound. We'll see what we learn, but certainly this class is exciting. In this current study, there are 32 patients who have been enrolled, risvodetinib is a once-daily drug, and we're going to learn more about how these patients did over the 12 week trial.

P2B001 one is a combination therapy drug that combines extended release pramipexole at low dose with extended release rasagiline low dose. The theory is that you can get the benefits by combining the medications at lower doses than you would by using them in separate doses. In the U.S. at least, there is no extended release rasagiline available. What they found in the pivotal trial was that in fact, you did get benefits with respect to UPDRS (Unified Parkinson's Disease Rating Scale) motor scores, using this combination therapy, rather than the individual components. What they're looking at now was some additional safety analysis to see if these drugs safe to use in combination. And what they found was that there was actually a lower number of adverse dopaminergic events with this combination therapy then with the separate components. This drug may be a reasonable option for early patients with Parkinson disease for once daily dosing, using combination therapy to get the benefits of the two drugs together without the side effects of having to use higher doses of the single drug.

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