Amneal Announces Complete Response Resubmission for Parkinson Therapy IPX203

Author(s):

IPX203, a novel, oral formulation of carbidopa/levodopa, had its new drug application supported by findings from the phase 3 RISE-PD study, where treated patients showed greater ON time than immediate-release CD/LD.

Chintu Patel

After receiving a complete response letter (CRL) from the FDA in July 2023, Amneal Pharmaceuticals has announced it has presented its complete response resubmission to the FDA for its investigational agent IPX203, an oral formulation of carbidopa/levodopa (CD/LD) extended-release capsules.¹

In the original CRL, the agency noted that the pharmacokinetic data for the safety of 1 ingredient, levodopa, was sufficient; however, it felt it needed additional data for the second ingredient, carbidopa. The resubmitted package now included additional information from a healthy volunteer study which was conducted in the further quarter of 2023. Amneal noted that the FDA did not request any other studies.

IPX203’s new drug application (NDA) was supported by findings from the phase 3 RISE-PD clinical trial (NCT0300788) which demonstrated the therapy’s ability to provide significantly more ON time per day than immediate-release (IR) CD/LD. The NDA was originally accepted in November 2022 and the full results of the trial were published in JAMA Neurology In August 2023, months after the CRL was issued.²

"We are pleased to provide our complete response resubmission for IPX203 as we look to expand our Parkinson franchise," Chirag and Chintu Patel, co-chief executive officer at Amneal, said in a statement.¹ "We look forward to launching this much-needed treatment in the second half of 2024, subject to FDA approval."

RISE-PD consisted of a 4-week screening period, a 3-week open-label IR CD/LD dose-adjustment period, a 4-week open-label IPX203 dose-conversion period, and a 13-week double-blind, double-dummy treatment period. Results from the trial showed that the agent met its primary end points, as those dosed with IPX203 (n = 256) 3 times per day had 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.²

Led by Robert A. Hauser, MD, director of the Parkinson’s and Movement Disorders Center at the University of South Florida, 449 patients (88.7%) completed the study. The secondary end point of change from baseline in OFF-time in hours per day showed that IPX203 treatment resulted in significantly less OFF-time compared with IR CD/LD (difference in least square [LS] means, –0.48; 95% CI, –0.90 to –0.06; P = .03). Between the groups, 29.7% and 18.8% of patients on IPX203 and IR CD/LD, respectively, rated themselves as much improved or very much improved on PGI-C (P = .002).

Among those treated with IPX203, the most frequently reported treatment emergent adverse events were nausea (4.3%), anxiety (2.7%), and dizziness (2.3%), while those on IR CD/LD mostly experienced fall (3.6%), urinary tract infection (3.2%), and back pain (2.8%). No clinically relevant treatment group differences were noted for laboratory parameters, vital signs, and electrocardiogram results. There were no deaths reported as well.

REFERENCES
1. Amneal Announces Complete Response Resubmission for IPX203 New Drug Application. News release. Amneal Pharmaceuticals. February 8, 2024. Accessed February 8, 2024. https://finance.yahoo.com/news/amneal-announces-complete-response-resubmission-210500452.html
2. Hauser RA, Espay AJ, Ellenbogen AL, et al. IPX203 vs immediate-release carbidopa-levodopa for the treatment of motor fluctuations in Parkinson disease: the RISE-PD randomized clinical trial. JAMA Neurol. Published online August 14, 2023. doi:10.1001/jamaneurol.2023.2679