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Crexont

Generic name: carbidopa and levodopa
Treatment for: Parkinson's Disease

Update: Crexont (carbidopa and levodopa) Now FDA Approved - August 7, 2024

Amneal Announces Submission of New Drug Application to the U.S. FDA for IPX203 for the Treatment of Parkinson’s Disease

BRIDGEWATER, N.J.--(BUSINESS WIRE) August 31, 2022 --Amneal Pharmaceuticals, Inc. (NYSE: AMRX) today announced it has submitted a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for IPX203, a novel, oral formulation of carbidopa/levodopa (CD/LD) extended-release capsules for the treatment of Parkinson’s disease (PD).

The submission is based on results from the pivotal Phase 3 RISE-PD clinical trial demonstrating more “Good On” time compared to immediate-release CD/LD, even when IPX203 was dosed on average three times per day and immediate-release CD/LD was dosed on average five times per day. The trial also showed that subjects on IPX203 demonstrated significantly less “Off” time compared with immediate-release CD/LD. A post-hoc analysis of the Least Squares Mean difference at end of study (week 20) showed that IPX203 provided 1.55 more hours of “Good On” time per dose versus immediate-release CD/LD, representing a 70% per dose increase.

“We are committed to furthering the advancement of treatments that can provide longer-lasting duration of benefit with every dose and simplify medication regimens,” said Chintu Patel, Co-Chief Executive Officer. “The RISE-PD data indicate IPX203 can offer patients a new and important treatment option that will enable them to have more “Good On” time during the day, which we believe would be a significant new benefit for Parkinson’s patients. We are working with the FDA to bring this treatment to market.”

Many people living with PD experience motor fluctuations as part of their symptoms. “On” time refers to periods when these symptoms are better controlled, and patients can move and function better. Extending “Good On” time and reducing “Off” time are often key goals for patients, caregivers and healthcare providers as this can provide more consistent symptom control throughout the day.

CD/LD has been the gold standard of treatment for PD since the 1970s, but additional options are needed that can help patients function more consistently with an increase in “Good On” time per dose. Based on data in the Amneal clinical trials, IPX203 can offer patients additional “Good On” time with reduced dose frequency compared to immediate-release CD/LD.

“We are very pleased to submit our NDA for IPX203,” said Chirag Patel, Co-Chief Executive Officer. “As leaders in the PD space, Amneal knows how important it is for patients to achieve more ‘Good On’ time and live each day the way they choose. We are confident IPX203 can help them accomplish that goal.”

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 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 IPX203. 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) or immediate-release CD/LD (with matching IPX203 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 earlier this year (2022).

About IPX203

IPX203 is a novel, oral formulation of CD/LD extended-release capsules designed for the treatment of Parkinson’s disease. IPX203 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, coated with a sustained release polymer to allow for slow release of the drug, a mucoadhesive polymer to keep the granules adhered to the area of absorption longer, and an enteric coating to prevent the beads 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 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 neurodegenerative disorder of the nervous system 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 essential medicines company. We make healthy possible through the development, manufacturing, and distribution of generic and specialty pharmaceuticals, primarily within the United States. The Company has a diverse portfolio of over 250 products in its Generics segment and is expanding across a broad range of complex products and therapeutic areas, including injectables and biosimilars. In its Specialty segment, Amneal has a growing portfolio of branded pharmaceutical products 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, 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 or forecasts for the future, including among other things: product research and development; discussions of future operations; expected operating results and financial performance; the Company’s strategy for growth; 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: 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; the impact of global economic conditions; direct or indirect impacts of the ongoing COVID-19 pandemic; our ability to obtain exclusive marketing rights for our products; the impact of 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, make and integrate acquisitions 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 impact of severe weather. 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.
Source: Amneal Pharmaceuticals, Inc.

Posted: August 2022

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