Impax Pharmaceuticals, the branded products division of Impax Laboratories, Inc. (NASDAQ: IPXL), today announced statistically significant, positive, top-line results of the ADVANCE-Parkinson's Disease (PD) Phase III clinical study of the safety and efficacy of IPX066 versus immediate-release (IR) carbidopa-levodopa (CD-LD) in advanced PD patients experiencing motor fluctuations. IPX066 is an investigational extended release (ER) CD-LD product. The ADVANCE-PD results demonstrated that IPX066 produced significantly improved control of motor symptoms as compared to IR CD-LD in multiple clinical measures in subjects with advanced PD.
The primary endpoint of this comparison study of IPX066 to IR CD-LD was the percentage of "off time" during waking hours. IPX066 demonstrated a 37% improvement from baseline for IPX066 vs. a 17% improvement from baseline for IR CD-LD (p<0.0001). "Off time" is the functional state when patients' medication effect has worn off and there is a return of Parkinson's symptoms.
The study enrolled 471 subjects on a stable regimen of IR CD-LD who were first entered into a dose-adjustment phase of their IR CD-LD, followed by a conversion to IPX066 after which they were then randomized to either IPX066 or IR CD-LD. Subjects converted to IPX066 experienced a reduction from baseline of more than 2 hours in total "off time" during waking hours, and this effect was maintained in the group then randomized to IPX066 during the blinded study portion. While the group treated with IR CD-LD achieved similar improvement during conversion to IPX066, "off time" worsened by 1.0 hours during double blind treatment with IR CD-LD (p<0.0001). In addition, during double-blind treatment, subjects experienced similar results in "on time" without troublesome dyskinesia with an increase of 1.9 hours for IPX066 compared to an increase of 0.8 hours for IR CD-LD as measured from study entry (p<0.001).
Additional clinical and patient-reported outcome measures in the study consistently demonstrate the improved IPX066 efficacy profile when compared to IR CD-LD. This includes the Unified Parkinson's Disease Rating Scale (UPDRS), Clinician Global Impression of Change (CGI) and Patient Global Impression of Change (PGI), which also demonstrated significant improvements in treatment with IPX066 compared to IR CD-LD (p<0.0001 for all comparisons). In quality-of-life (QOL) measures, IPX066 demonstrated significant improvement over IR CD-LD as measured by PDQ-39 (p<0.035) and modified Rankin Test (p<0.006).
"Impax Pharmaceuticals is excited to report these positive results for the ADVANCE-PD trial demonstrating the clinical benefits of IPX066 over IR CD-LD, which is the gold standard in treating advanced PD," stated Dr. Suneel Gupta, Impax Pharmaceuticals' Chief Scientific Officer. "Consistent with our Phase II findings, these data show IPX066 provides a robust level of efficacy across a range of PD clinical and QOL measures, which represents a potentially significant improvement over existing treatment options. With the successful completion of this ADVANCE-PD trial and the APEX-PD trial in patients with early PD, we have completed the two required Phase III trials for a New Drug Application (NDA) as agreed with the Food and Drug Administration. We are working diligently to file an NDA in the fourth quarter of 2011."
IPX066 was generally well tolerated, and during the double-blind portion of the trial had an adverse event (AE) rate of 43% compared to 40% for IR CD-LD. The most common AEs reported for IPX066 included: insomnia, nausea, fall, dizziness, and dyskinesia (no event was associated with a greater than 3.5% overall incidence). The rate of related serious AEs was comparable, with one subject in each treatment arm reporting serious treatment-related AEs in the double-blind treatment phase.
According to Robert A. Hauser, MD, Professor of Neurology, Molecular Pharmacology, and Physiology and Director of the Parkinson's Disease & Movement Disorders Center at the University of South Florida and an ADVANCE-PD study investigator, "There is a major unmet need in patients with advanced PD for a therapy that can consistently extend and improve motor symptom control through the day and enhance quality of life." Dr. Hauser added, "In the ADVANCE-PD study, daily "off time" was reduced without worsening of dyskinesia, and both patients and clinicians reported overall improvement. The magnitude of benefit observed with IPX066 was clinically significant and results indicate that PD patients should be able to enjoy improved control of their motor symptoms and a better quality of life."
Impax Pharmaceuticals plans to present complete results of the ADVANCE-PD study at an upcoming scientific meeting.
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