Amneal Announces Positive Topline Results from Pivotal Phase 3 RISE-PD Clinical Trial of IPX-203 in Patients with Parkinson’s Disease Who Experience Motor Fluctuations

Rhea-AI Summary

Amneal Pharmaceuticals (NYSE: AMRX) announced positive topline results from its pivotal Phase 3 RISE-PD clinical trial for IPX-203, a novel formulation for Parkinson’s disease. The trial met its primary endpoint, showing an increase of 0.53 hours in “Good On” time compared to immediate-release CD/LD (p=0.0194). A New Drug Application submission to the FDA is planned for mid-2022. The trial involved 506 patients across 108 sites, demonstrating the drug's efficacy and safety, with 29.7% of patients reporting significant improvements (p=0.0015).

Positive

• Demonstrated 0.53 hours increase in 'Good On' time compared to immediate-release CD/LD (p=0.0194).
• 29.7% of patients showed significant improvement in PGI-C scores (p=0.0015).
• NDA submission planned for mid-2022, indicating progress towards market entry.

Negative

• 3.1% of patients in the IPX-203 group reported serious adverse events.
• Treatment-emergent adverse events were higher in IPX-203 (42.2%) compared to immediate-release CD/LD (31.6%).

- Study was successful in demonstrating statistically significant improvement in efficacy for IPX-203 compared to immediate-release CD/LD, even when IPX-203 was dosed on average three times per day and immediate-release CD/LD was dosed on average five times per day

- New Drug Application submission to the FDA planned for mid-2022

- Company to host conference call to discuss trial results today at 4:30 p.m. ET

BRIDGEWATER, N.J.--(BUSINESS WIRE)-- Amneal Pharmaceuticals, Inc. (NYSE: AMRX) today announced positive topline results from the pivotal Phase 3 RISE-PD clinical trial that evaluated the novel formulation, IPX-203, in patients with Parkinson’s disease (PD) who have motor fluctuations. The trial met its primary endpoint, demonstrating superior “Good On” time from baseline in hours per day at the end of the 13-week double-blind treatment period with IPX-203 CD/LD extended-release capsules compared with immediate-release CD/LD. Based on these topline results plus other supportive data, Amneal plans to submit a New Drug Application (NDA) for IPX-203 with the U.S. Food and Drug Administration (FDA) in mid-2022.

Phase 3 topline results showed the study was successful in demonstrating statistically significant improvement in efficacy for IPX-203 compared to immediate-release CD/LD, even when IPX-203 was dosed on average 3 times per day and immediate-release CD/LD was dosed on average 5 times per day. IPX-203 treatment resulted in 0.53 more hours of “Good On” time than immediate-release CD/LD (p=0.0194), when comparing change from baseline (Week 7) in both study arms.

The secondary endpoint for change from baseline in “Off” time showed IPX-203 resulted in significantly less “Off” time compared with immediate-release CD/LD (-0.48 hr, p=0.0252). In addition, analysis of the secondary endpoint for Patients' Global Impression of Change (PGI-C) scores showed 29.7% of patients treated with IPX-203 were “much improved” or “very much improved” compared with 18.8% of patients treated with immediate-release CD/LD (p=0.0015). IPX-203 change from baseline scores for Movement Disorder Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part III or sum of MDS-UPDRS Part II and III were similar to those of immediate-release CD/LD.

A post-hoc analysis of Least Squares Mean difference at Week 20 (EOS/ET) showed IPX-203 increased “Good On” time by 1.55 hours per dose compared with immediate-release CD/LD (p<0.0001).

Table 1. RISE-PD efficacy results: Primary and key secondary endpoints

	Week 0 Enrollment	Week 7 Baseline (Randomization)	Week 20 End of Study (or Early Termination)	p-value
Mean “Good On” time (h)
IPX-203	9.46	11.67	11.35	0.0194∆
immediate-release CD/LD	9.61	11.72	10.77
Mean “Off” time (h)
IPX-203	6.15	3.95	4.18	0.0252∆
immediate-release CD/LD	6.05	4.02	4.75
Percentage of patients who reported “much improved” or “very much improved” scores on the PGI-C scale
IPX-203	N/A	N/A	29.7%	0.0015□
immediate-release CD/LD	N/A	N/A	18.8%
Mean MDS-UPDRS part III score
IPX-203	29.6	26.9	27.8	0.9587∆
immediate-release CD/LD	29.7	27.0	28.0
Mean MDS-UPDRS Sum of part II + III score
IPX-203	42.9	38.9	40.6	0.9668∆
immediate-release CD/LD	42.9	39.3	41.1

∆ = p-value based on change from Week 7 (Baseline) to Week 20 (End of Study or Early Termination [EOS/ET])

□ = p-value based on comparison of treatments at Week 20 (EOS/ET)

The trial was conducted at 108 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 with PD age 40 and older. The study design was reviewed by the FDA and conducted pursuant to a Special Protocol Assessment.

In the randomized patient population, eight (3.1%) subjects reported serious adverse events (SAEs) in the IPX-203 study arm and four (1.6%) subjects reported SAEs in the immediate-release CD/LD arm. Treatment-emergent adverse events (TEAEs) were reported for both study arms (108 [42.2%] for IPX-203, 79 [31.6%] for immediate-release CD/LD). The most common AEs (≥3%) were nausea, dry mouth, urinary tract infection, and fall.

“Despite the introduction of several new medications for Parkinson’s disease in recent years, new treatment options are needed that provide longer-lasting duration of benefit with each dose and simplify medication regimens for patients affected by this devastating disease,” Alberto Espay, MD, FAAN, Professor of Neurology at the University of Cincinnati, Director of James J. and Joan A. Gardner Family Center, and Research Chair for Parkinson’s Disease and Movement Disorders.

“The topline data from RISE-PD indicates that IPX-203 has the potential to offer patients superior ‘Good On’ time with reduced dosing frequency, compared to immediate-release CD/LD,” 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.

“These positive data from the Phase 3 trial of IPX-203 represent a substantial step forward in strengthening Amneal’s Specialty Pharma portfolio, which is heavily focused on medicines for central nervous system disorders,” said Chirag and Chintu Patel, Co-Chief Executive Officers, Amneal. “We look forward to submitting an NDA with the FDA and potentially making this treatment available to the PD community.”

Conference Call Details
Amneal will host a conference call today, Wednesday, August 25, 2021, at 4:30 p.m. ET that will feature members of Amneal’s management team as well as Alberto Espay, MD, MSc, FAAN, FANA (University of Cincinnati), and Robert A Hauser, MD, MBA, FAAN (University of South Florida) to discuss topline results from the pivotal Phase 3 RISE-PD clinical trial. The presentation will be followed by a live Q&A session.

Please visit https://lifesci.rampard.com/WebcastingAppv5/Events/eventsDispatcher.jsp?Y2lk=MTM2Mg== to register and access the live webinar. A replay will be made available on the company’s website for six months. The presentation materials will be posted on the Investor Relations website following the conclusion of the event.

About the Pivotal Phase 3 RISE-PD Trial
The multicenter, randomized, double-blind, double-dummy, active-controlled, parallel-group RISE-PD trial evaluated the efficacy and safety of IPX-203 CD/LD extended-release capsules compared with immediate-release 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 IPX-203 (with matching immediate-release CD/LD placebo) or immediate-release CD/LD (with matching IPX-203 placebo). Baseline for all endpoints was Week 7 (Visit 4), which occurred pre-randomization.

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 108 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 with PD age 40 and older. The study design was reviewed by the FDA and conducted pursuant to a Special Protocol Assessment. A nine-month safety extension study is ongoing.

About IPX-203
IPX-203 is a novel, oral formulation of CD/LD extended-release capsules for patients with PD who have motor fluctuations. IPX-203 was developed with an innovative formulation that contains immediate-release and extended-release granules, and mucoadhesive polymers, to provide rapid absorption and maximize levodopa absorption. 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 Amneal
Amneal Pharmaceuticals, Inc. (NYSE: AMRX), headquartered in Bridgewater, NJ, is a fully-integrated pharmaceutical company focused on the development, manufacturing and distribution of generic and specialty drug products. The Company has operations in North America, Asia, and Europe, working together to bring high-quality medicines to patients primarily within the United States.

Amneal has an extensive portfolio of approximately 250 generic product families and is expanding its portfolio to include complex dosage forms, including biosimilars, in a broad range of therapeutic areas. The Company also markets a portfolio of branded pharmaceutical products through its Specialty segment focused principally on central nervous system and endocrine disorders.

The Company also owns 65% of AvKARE. AvKARE provides pharmaceuticals, medical and surgical products and services primarily to governmental agencies, primarily focused on serving the Department of Defense and the Department of Veterans Affairs. AvKARE is also a packager and wholesale distributor of pharmaceuticals and vitamins to its retail and institutional customers who are located throughout the United States focused primarily on offering 340b-qualified entities products to provide consistency in care and pricing. For more information, visit www.amneal.com.

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 or forecasts for the future, including among other things: discussions of future operations; expected operating results and financial performance; impact of planned acquisitions and dispositions; the Company’s strategy for growth; product development; regulatory approvals; market position and expenditures. Words such as “plans,” “expects,” “will,” “anticipates,” “estimates” and similar words 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. 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: the impact of the COVID-19 pandemic; the impact of global economic conditions; our ability to successfully develop, license, acquire and commercialize new products on a timely basis; our ability to obtain exclusive marketing rights for our products; 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 manage our growth through acquisitions and otherwise; our dependence on the sales of a limited number of products for a substantial portion of our total revenues; 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 FDA product approval requirements; risks related to federal regulation of arrangements between manufacturers of branded and generic products; the impact of healthcare reform and changes in coverage and reimbursement levels by governmental authorities and other third-party payers; the continuing trend of consolidation of certain customer groups; our reliance on certain licenses to proprietary technologies from time to time; our dependence on third-party suppliers and distributors for raw materials for our products and certain finished goods; our dependence on third-party agreements for a portion of our product offerings; our ability to identify and make acquisitions of or investments in complementary businesses and products on advantageous terms; legal, regulatory and legislative efforts by our brand competitors to deter competition from our generic alternatives; the significant amount of resources we expend on research and development; 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; 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.

View source version on businesswire.com: https://www.businesswire.com/news/home/20210825005679/en/

Investor Contact

Anthony DiMeo

Senior Director, Investor Relations

anthony.dimeo@amneal.com

Media Contact

Julie Normart

Group Director, Media and Engagement, Real Chemistry

jnormart@realchemistry.com

Amneal Medical Affairs

888-990-AMRX (2679)

askamrx@amneal.com

Source: Amneal Pharmaceuticals, Inc.

FAQ

What were the Phase 3 trial results for AMRX's IPX-203?

The Phase 3 RISE-PD trial showed a statistically significant increase of 0.53 hours in 'Good On' time for IPX-203 compared to immediate-release CD/LD.

When is Amneal Pharmaceuticals planning to submit the NDA for IPX-203?

Amneal plans to submit the New Drug Application for IPX-203 to the FDA in mid-2022.

What are the next steps for IPX-203 after the trial?

Following the successful trial results, Amneal will submit an NDA to the FDA and continue its development for market availability.

How many patients were involved in the RISE-PD trial?

The RISE-PD trial included 506 patients with Parkinson's disease across 108 clinical sites.

What percentage of patients reported improvement in the RISE-PD trial?

29.7% of patients treated with IPX-203 reported being 'much improved' or 'very much improved'.