At the American Academy of Neurology (AAN) 2023 Annual Meeting, Amneal presented new data evaluating IPX203 (carbidopa + levodopa, CD/LD) in a nine-month open-label extension (OLE) study in Parkinson’s disease (PD) patients with motor fluctuations (NCT03877510). The OLE study involved 419 participants who completed the Phase III RISE-PD (NCT03670953). This data highlights that IPX203 could offer an additional safe and tolerable extended-release formulation of CD/LD and could offer an overall better quality of life in moderate to advanced-stage PD patients. IPX203 is currently under review by the FDA for the treatment of PD, with a PDUFA date of 30 June 2023.
Levodopa has been the gold standard for patients with PD for over 50 years. In the early stages of the disease, symptoms are well managed by levodopa, but as the disease progresses, reliable dosing becomes more difficult. Most patients on levodopa for an average of five years may experience motor complications. Levodopa is a particularly difficult compound due to limitations in its absorption combined with a short half-life. Peaks and troughs in levodopa plasma concentration are responsible for peak-dose dyskinesia and off-episodes, respectively, two of the most common motor complications. Furthermore, as PD progresses, dopaminergic neurons die off, the window of optimal levodopa plasma concentration is narrowed, and motor fluctuations begin to emerge. According to key opinion leaders (KOLs) previously interviewed by GlobalData, as many as one-third of PD patients experience dyskinesia and almost all of them will eventually have off-episodes. As such, moderate and advanced-stage PD patients, who require a continuous supply of levodopa, are usually prescribed oral sustained-release formulations such as Amneal’s Rytary (LD/CD) and Roche’s Madopar CR.
IPX203 is an extended-release formulation that consists of a combination of immediate-release (IR) CD/LD granules and extended-release (ER) beads of levodopa. The ER beads are coated with a sustained-release polymer to allow for slow drug release, a mucoadhesive polymer to keep the beads adhered to the area of absorption longer, and an enteric coating to prevent the beads from disintegrating too early in the stomach. In the RISE-PD study, IPX203 met the study’s primary endpoint by demonstrating a statistically significant improvement in efficacy for IPX203 compared to IR CD/LD. IPX203 treatment resulted in 0.53 more hours of “Good On” time than IR CD/LD when comparing change from baseline in both study arms. “Good On” time is defined as the total time with either non-troublesome dyskinesia symptoms or duration without dyskinesia.
In the OLE study data presented at the AAN 2023, the magnitude of efficacy obtained with IPX203 was sustained in patients from baseline to the end of the OLE study. In the study, 52.7% of subjects experienced treatment-emergent adverse events (TEAEs). Most TEAEs were either mild or moderate in severity and occurred within the first 90 days of treatment. Of them, the most common were dyskinesia (5.0%), fall (5.0%), urinary tract infection (5.0%), back pain (3.6%), and constipation (2.6%).
However, some KOLs indicated that the improvement in efficacy with IPX203 compared with IR CD/LD was not significant to impact their treatment patterns, particularly if IPX203 is anticipated to have premium pricing. But IPX203 could be an option for patients who have not had a good experience with Rytary. A further competitive threat to the future of IPX203 and other oral LD/CDs is the development of novel subcutaneous levodopa delivery systems. KOLs showed great enthusiasm for AbbVie’s ABBV-951 and NeuroDerm’s ND0612, which enable continuous infusion of LD/CD and could create additional options to control various motor complications in moderate to advanced-stage patients.