Amneal Submits New Drug Application to the US FDA for IPX203 for the Treatment of Parkinson's Disease
6 September 2022 - - US-based generic and specialty pharmaceuticals company Amneal Pharmaceuticals, Inc. (NYSE: AMRX) has submitted a New Drug Application to the US Food and Drug Administration for IPX203, a novel, oral formulation of carbidopa/levodopa (CD/LD) extended-release capsules for the treatment of Parkinson's disease, the company said.

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.

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.

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.

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 US 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.

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.

Parkinson's disease has become the fastest growing neurological disorder worldwide, with approximately 1m patients diagnosed in the US.

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.

While PD is not considered a fatal disease, it is associated with significant morbidity and disability.

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.

Amneal Pharmaceuticals, Inc. (NYSE: AMRX), headquartered in Bridgewater, NJ, is engaged in the development, manufacturing, and distribution of generic and specialty pharmaceuticals, primarily within the United States.