• IPX203 demonstrated statistically significant improvement in daily “Good On” time compared to optimized IR CD/LD, with fewer daily doses

BRIDGEWATER, N.J. / Aug 24, 2023 / Business Wire / Amneal Pharmaceuticals, Inc. (NYSE: AMRX) today announced that JAMA Neurology has published results from the RISE-PD clinical study assessing the efficacy and safety of IPX203 versus optimized immediate-release carbidopa/levodopa (IR CD/LD) for the treatment of Parkinson’s disease (PD). The study met its primary and secondary endpoints finding that IPX203 provided more hours of “Good On” time per day, less “Off” time per day, and more “Good On” time per dose than optimized IR CD/LD, even when dosed less frequently. “Good On” time is defined as the sum of “On” time without dyskinesia and “On” time with non-troublesome dyskinesia. The manuscript titled, “IPX203 vs Immediate-Release Carbidopa-Levodopa for the Treatment of Motor Fluctuations in Parkinson Disease,” was published online on August 14, 2023.

“When it comes to Parkinson’s disease, the community is looking for treatments that provide a longer duration of benefit per dose of LD and simplified dosing regimens,” said Robert A. Hauser, M.D., Professor of Neurology at the University of South Florida and Director of the Parkinson's Disease and Movement Disorders Center. “We are very encouraged by the recently published data in JAMA Neurology which illustrate how IPX203 could fill this need, potentially leading to a better patient experience, more ‘Good On’ time, and improved patient adherence.”

RISE-PD was a 20-week, randomized, double-blind, double-dummy, active-controlled, phase 3 clinical trial. A total of 630 patients (mean age 66.5 years; 62.9% men) were enrolled and 506 patients were randomly assigned to receive IPX203 (n = 256) or immediate-release carbidopa-levodopa (n = 250). The results published in JAMA Neurology show that treatment with IPX203 demonstrated statistically significant improvement in daily “Good On” time with fewer doses of IPX203 compared with immediate-release carbidopa-levodopa (least squares mean, 0.53 hours; 95% CI, 0.09-0.97), with IPX203 dosed a mean three times per day vs 5 times per day for immediate-release carbidopa-levodopa.

Additionally, “Good On” time per dose increased by 1.55 hours with IPX203 compared with immediate-release carbidopa-levodopa (95% CI, 1.37-1.73). IPX203 was well tolerated. The most frequently reported TEAEs among patients treated with IPX203 were nausea (11 [4.3%]), anxiety (7 [2.7%]), and dizziness (6 [2.3%]). The most frequently reported TEAEs among patients treated with IR CD-LD were fall (9 [3.6%]), urinary tract infection (8 [3.2%]), and back pain (7 [2.8%]).

“Our commitment to people living with Parkinson’s disease, and advancing treatments designed to provide longer-lasting duration of benefit and simpler medication regimens, remains unchanged,” said Chirag and Chintu Patel, Co-Chief Executive Officers. “The data published in JAMA Neurology illustrate that IPX203 may provide sustained benefit throughout the day, with more ‘Good On’ time with fewer daily doses – which could represent an important advance for people living with Parkinson’s disease.”

Following a Complete Response Letter (CRL) from the FDA earlier this year on its New Drug Application for IPX203, Amneal has shared a reanalysis of the data and requested a Type A meeting as it looks to bring the treatment to market.

About the RISE-PD Trial

The multicenter, randomized, double-blind, double-dummy, active-controlled, parallel-group RISE-PD trial evaluated the efficacy and safety of IPX203 CD/LD extended-release capsules compared with IR CD/LD in the treatment of patients with PD who have motor fluctuations.

The trial consisted of a 3-week, open-label immediate-release CD/LD dose adjustment period and a 4-week, open-label period for conversion to IPX-203. This was followed by a 13-week double-blind treatment period in which patients were randomized 1:1 to receive either IPX203 (with matching immediate-release CD/LD placebo) optimized IR CD/LD (with matching IPX-203 placebo). Baseline for all endpoints was Week 7 (Visit 4), which occurred pre-randomization. The most common adverse reaction (incidence ≥ 3% and greater than immediate-release CD/LD) was nausea (4.3%).

The primary endpoint of the trial assessed the change from baseline in “Good On” time in hours per day at the end of the double-blind treatment period (Week 20 or early termination). “Good On” time is defined as the sum of “On” time without dyskinesia and “On” time with non-troublesome dyskinesia. Secondary endpoints assessed the change from baseline in “Off” time in hours per day, proportion of patients who were either “much improved” or “very much improved” in Patients' Global Impression of Change (PGI-C) scores, change from baseline in the Movement Disorder Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III score, and the change from baseline in sum of MDS-UPDRS Parts II and III scores.

The trial was conducted at 105 clinical sites in the U.S. and European countries, including Czechia, France, Germany, Italy, Poland, Spain and the United Kingdom. The study randomized 506 patients who had received a PD diagnosis at age 40 or older. The study design was reviewed by the FDA and conducted pursuant to a Special Protocol Assessment. A nine-month safety extension study was completed in 2022.

About IPX203

IPX203 is a novel, oral formulation of CD/LD extended-release capsules designed for the treatment of Parkinson’s disease. IPX-203 contains immediate-release granules and extended-release coated beads. The IR granules consist of CD and LD, with a disintegrant polymer to allow for rapid dissolution. The ER beads consist of LD, a mucoadhesive polymer to keep the granules adhered to the area of absorption longer, and an enteric coating to prevent the granules from disintegrating prematurely in the stomach. This formulation is distinct from RYTARY^® (carbidopa/levodopa) extended-release capsules, Amneal’s extended-release CD/LD treatment for PD approved by the U.S. FDA in 2015.

About Parkinson’s Disease

Parkinson’s disease (PD) has become the fastest growing neurological disorder worldwide, with approximately 1 million patients diagnosed in the U.S.^1,2 It is a progressive disorder of the central nervous system (CNS) that affects dopamine-producing neurons in the brain that affect movement.

PD is characterized by slowness of movement, stiffness, resting tremor and impaired balance.³ While PD is not considered a fatal disease, it is associated with significant morbidity and disability.⁴ The average age at diagnosis for patients with PD is 60; as people live longer, the number of patients living with PD is predicted to grow significantly over the coming decades.^1,5

About Amneal

Amneal Pharmaceuticals, Inc. (NYSE: AMRX), headquartered in Bridgewater, NJ, is a fully integrated global pharmaceuticals company. We make healthy possible through the development, manufacturing, and distribution of a diverse portfolio of approximately 270 pharmaceutical products, primarily within the United States. In its Generics segment, the Company is expanding across a broad range of complex product categories and therapeutic areas, including injectables and biosimilars. In its Specialty segment, Amneal has a growing portfolio of branded pharmaceuticals focused primarily on central nervous system and endocrine disorders, with a pipeline focused on unmet needs. Through its AvKARE segment, the Company is a distributor of pharmaceuticals and other products for the U.S. federal government, retail, and institutional markets. For more information, please visit www.amneal.com.

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References:

1. Dorsey ER et al. JAMA Neurol. 2018;75(1):9-10.
2. Marras et al. NPJ Parkinsons Dis. 2018;4:21.
3. NINDS. Parkinson’s disease: challenges, progress, and promise. Reviewed August 2019. Accessed April 16, 2021.
4. Data Monitor: Gibrat et al., 2009; Goldenberg, 2008; Muangpaisan et al., 2009; Pringsheim et al., 2014.
5. John Hopkins Medicine. Young-Onset Parkinson’s disease. Accessed August 17, 2021.