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

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.

Cautionary Statement on Forward-Looking Statements

Certain statements contained herein, regarding matters that are not historical facts, may be forward-looking statements (as defined in the U.S. Private Securities Litigation Reform Act of 1995). Such forward-looking statements include statements regarding management’s intentions, plans, beliefs, expectations, financial results, or forecasts for the future, including among other things: discussions of future operations, including international expansion; expected or estimated operating results and financial performance; the Company’s growth prospects and opportunities as well as its strategy for growth; product development and launches; the successful commercialization and market acceptance of new products, and other non-historical statements. Words such as “plans,” “expects,” “will,” “anticipates,” “estimates,” and similar words, or the negatives thereof, are intended to identify estimates and forward-looking statements.

The reader is cautioned not to rely on these forward-looking statements. These forward-looking statements are based on current expectations of future events, including with respect to future market conditions, company performance and financial results, operational investments, business prospects, new strategies and growth initiatives, the competitive environment, and other events. If the underlying assumptions prove inaccurate or known or unknown risks or uncertainties materialize, actual results could vary materially from the expectations and projections of the Company.

Such risks and uncertainties include, but are not limited to: our ability to successfully develop, license, acquire and commercialize new products on a timely basis; the competition we face in the pharmaceutical industry from brand and generic drug product companies, and the impact of that competition on our ability to set prices; our ability to obtain exclusive marketing rights for our products; our ability to manage our growth through acquisitions and otherwise; our revenues are derived from the sales of a limited number of products, a substantial portion of which are through a limited number of customers; the continuing trend of consolidation of certain customer groups; our dependence on third-party suppliers and distributors for raw materials for our products and certain finished goods; our substantial amount of indebtedness and our ability to generate sufficient cash to service our indebtedness in the future, and the impact of interest rate fluctuations on such indebtedness; our ability to secure satisfactory terms when negotiating a refinancing or other new indebtedness; our dependence on third-party agreements for a portion of our product offerings; legal, regulatory and legislative efforts by our brand competitors to deter competition from our generic alternatives; risks related to federal regulation of arrangements between manufacturers of branded and generic products; our reliance on certain licenses to proprietary technologies from time to time; the significant amount of resources we expend on research and development; the risk of product liability and other claims against us by consumers and other third parties; risks related to changes in the regulatory environment, including U.S. federal and state laws related to healthcare fraud abuse and health information privacy and security and changes in such laws; changes to Food and Drug Administration product approval requirements; the impact of healthcare reform and changes in coverage and reimbursement levels by governmental authorities and other third-party payers; our potential expansion into additional international markets subjecting us to increased regulatory, economic, social and political uncertainties, including recent events affecting the financial services industry; our ability to identify, make and integrate acquisitions or investments in complementary businesses and products on advantageous terms; the impact of global economic, political or other catastrophic events; our ability to attract, hire and retain highly skilled personnel; our obligations under a tax receivable agreement may be significant; and the high concentration of ownership of our Class A Common Stock and the fact that we are controlled by the Amneal Group. The forward-looking statements contained herein are also subject generally to other risks and uncertainties that are described from time to time in the Company’s filings with the Securities and Exchange Commission, including under Item 1A, “Risk Factors” in the Company’s most recent Annual Report on Form 10-K and in its subsequent reports on Forms 10-Q and 8-K. Investors are cautioned not to place undue reliance on any such forward-looking statements, which speak only as of the date they are made. Forward-looking statements included herein speak only as of the date hereof and we undertake no obligation to revise or update such statements to reflect the occurrence of events or circumstances after the date hereof.

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.

View source version on businesswire.com: https://www.businesswire.com/news/home/20230824209527/en/