Robert A. Hauser, MD, MBA, director of the Parkinson’s and Movement Disorders Center at the University of South Florida, provided insight on the therapeutic potential of IPX203, and why it adds flexibility to the treatment of Parkinson disease.
Later this month, the FDA will make a decision on IPX203 (Amneal Pharmaceuticals), an investigational extended-release carbidopa/levodopa (CD-LD) agent, as a potential treatment for patients with Parkinson disease (PD). For years, CD-LD has been the standard option to improve OFF and ON time in patients with the neurodegenerative disorder.
The agent’s new drug application was supported by findings from the phase 3 RISE-PD study (NCT03670953), which consisted of a 3-week, open-label dose adjustment phase, followed by a 4-week open-label conversion to IPX203, and a 13-week double blind maintenance phase. IPX203 was administered every 8 hours for most patients, although dosing intervals varied. In a follow-up analysis of the study, mean daily dosing frequency and most frequent LD dose were similar at the start and end of the conversion period, with stable dosing achieved in 1.6 (SD, 1.74) titration steps.
Presented at the 2nd Annual Advanced Therapeutics in Movement and Related Disorders (ATMRD) Congress, held by the PMD Alliance from June 8 to 11, 2023, in Washington, DC, data look at the dose conversion from immediate-release (IR) CD-LD to IPX203. For doses up to 250 mg LD, a conversion ratio of 2.8 from the most frequent individual IR CD-LD dose was deemed an appropriate starting dose of IPX203. As part of NeurologyLive’s coverage of the meeting, Robert A. Hauser, MD, MBA, an investigator on RISE-PD, sat down to discuss the clinical utility of IPX203, and why it serves as a promising therapy for patients with PD.
NeurologyLive®: What is the clinical significance of this data?
Robert Hauser, MD, MBA: This was an additional analysis of the RISE-PD trial which compared IPX203 to immediate release carbidopa levodopa. The outcome measures that were evaluated here included the duration of continuous good ON time, or time without troublesome dyskinesia. This is when patients are getting a good response and they don't have enough dyskinesia that's causing a negative effect. This is where we want patients to be as much of the day as possible. What we saw was that IPX203 compared to immediate release carbidopa levodopa provided 0.92 hours longer continuous good ON episodes through the day. It’s these good ON episodes throughout day that are when patients can function well, when they get their activities done. The longer we can get those episodes, the better for patients.
Were there any findings that stood out to you more than others?
We didn't look at it in this particular abstract [presented], but I think one of the most important analyses that we did was good ON time per dose, because that is a reflection of what this medication does for patients. In that analysis, we saw the IPX203 compared with immediate release carbidopa levodopa increased the good ON time per dose by 1.5 hours. Again, that shows the extent of good benefit that each administration provides, with the increasing good benefit per dose for patients.
How would you describe the safety profile?
There were a slightly increased [rate of] adverse events with IPX203 compared with IR in the maintenance period, and that included slight increase of dyskinesia as well.
If approved, how does this therapy fit in the treatment landscape?
IPX203 is going to be a very important treatment for patients with motor fluctuations and OFF episodes. It will allow patients to decrease OFF time and take fewer administrations of levodopa through the day.
Are there certain patients who may benefit more from it than others?
I think it should be considered an any patient who has OFF time. It'll probably be of most benefit for patients who still get a good response to levodopa, for patients who are taking more than 3 or 4 IR doses per day, and probably for patients who don't have very much dyskinesia, those patients would benefit the most. But I would still consider it in any patient who has OFF time through the day.
Is there anything else you’d like to add?
We continue to make advances in providing more good ON time throughout the day for patients. This includes these long-acting levodopa oral medications. In addition, there are subcutaneous infusions that are coming, and we also have our ongoing armament of adjunct medications. When you take all of these together, I think we should be doing much better than we had in the past with regard to reducing OFF time and increasing good ON time through the day.
Transcript edited for clarity. Click here for more coverage of the 2023 ATMRD Congress.