AAN 2023: IPX203 still safe, effective in extension study
Amneal shares update of experimental treatment in Phase 3 RISE-PD trial
IPX203, Amneal Pharmaceuticals‘ investigational extended-release carbidopa/levodopa (CD/LD) treatment for Parkinson’s disease, continued to exhibit a favorable safety and efficacy profile during the open-label extension part of the Phase 3 RISE-PD trial.
“IPX203 remained as efficacious and safe as it was shown during the RISE-PD study, and the vast majority of subjects reached a stable dose by about three months,” Alberto Espay, MD, of the University of Cincinnati, in Ohio, said in an oral presentation at the American Academy of Neurology (AAN) 2023 Annual Meeting, held April 22-27 in Boston, Massachusetts, and virtually.
Espay’s presentation was titled, “Long-term Safety and Efficacy of IPX203 in Parkinson’s Disease Patients with Motor Fluctuations: A 9-Month Open-label Extension Trial.”
The experimental treatment is under regulatory review with the U.S. Food and Drug Administration (FDA). The agency is expected to make a decision for IPX203’s approval by June 30.
CD/LD combination therapy is a mainstay treatment for Parkinson’s disease. Levodopa works to increase levels of dopamine, the brain chemical that’s lacking in Parkinson’s, while carbidopa helps to prevent levodopa’s breakdown.
Still, over time patients may develop “off” periods, or times when symptoms reappear between doses.
IPX203 is an extended-release oral formulation of CD/LD consisting of instant-release granules that provide immediate effects of levodopa, in addition to slow-release beads that enable sustained exposure to the medication.
By lasting longer in the bloodstream than immediate-release formulations of CD-LD, IPX203 is expected to help prevent “off” episodes and enable longer periods of “good on” time when symptoms are controlled well without troublesome involuntary movements, or dyskinesia.
Data from Phase 3 RISE-PD
Anneal’s application to the FDA was backed by data from the Phase 3 RISE-PD trial (NCT03670953), which enrolled 506 advanced Parkinson’s patients, ages 40 and older, who were experiencing “off” episodes at 105 sites in the U.S. and Europe.
After a dose adjustment phase with both therapies, participants were assigned randomly to receive IPX203 or immediate-release CD/LD oral tablets for 13 weeks (about three months).
Top-line results showed that IPX-203 was associated with significantly more “good on” time and less “off” time compared with the immediate-release therapy. While the instant-release formulation was dosed on average five times per day, IPX203 was required an average of three times daily.
Espay’s presentation concerned data from an open-label extension (OLE) phase (NCT03877510) that followed the trial, in which 419 participants were enrolled and received IPX203 for up to an additional nine months.
Patients received IPX203 two to four times per day, with doses six to 12 hours apart.
Most participants (70%) achieved a stable dose of IPX203 after three months in the OLE, with a mean daily dosing frequency of 3.1 times per day and mean daily dose of 1,539 mg.
Expected side effects
IPX203 was tolerated well, with the observed side effects being “consistent with the kinds of side effects that you would expect in dopaminergic medications,” Espay noted.
The most common side effects, which usually were mild or moderate, included falls (5%), dyskinesia (5%), and urinary tract infections (5%). Of these, only dyskinesia was considered treatment-related.
The efficacy of IPX203 remained consistent throughout the OLE, with scores on the Movement Disorder Society — Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) and its subscales remaining stable throughout the study. MDS-UPDRS is designed to assess the severity of Parkinson’s motor and non-motor symptoms and their effects on daily life.
“Patients who had any given degree of improvement largely kept it throughout the nine-month study,” Espay said. “Stability was the name of the game here.”
Ultimately, 16% of participants discontinued treatment early, which was due to adverse events in about 30% of cases and lack of effectiveness in another 20%.
The findings overall emphasize that the results from RISE-PD are “likely the ones that we will see in terms of clinical practice,” Espay concluded.
Note: The Parkinson’s News Today team is providing coverage of the American Academy of Neurology (AAN) 2023 Annual Meeting April 22-27. Go here to see the latest stories from the conference.