Benzinga | Aug 25, 2021 04:03PM EDT

Amneal Announces Topline Results From Pivotal Phase 3 RISE-PD Clinical Trial Of IPX-203 In Patients With Parkinson's Disease Who Experience Motor Fluctuations

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 Week 7 Week 20

Enrollment Baseline End of Study p-value (Randomization) (or Early Termination)

Mean "Good On" time (h)

IPX-203 9.46 11.67 11.35

immediate-release CD/ 9.61 11.72 10.77 0.0194?LD

Mean "Off" time (h)

IPX-203 6.15 3.95 4.18

immediate-release CD/ 6.05 4.02 4.75 0.0252?LD

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%

immediate-release CD/ N/A N/A 18.8% 0.0015?LD

Mean MDS-UPDRS part III score

IPX-203 29.6 26.9 27.8

immediate-release CD/ 29.7 27.0 28.0 0.9587?LD

Mean MDS-UPDRS Sum of part II + III score

IPX-203 42.9 38.9 40.6

immediate-release CD/ 42.9 39.3 41.1 0.9668?LD

= 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."