GSK and Impax announce positive topline results of ASCEND-PD Phase III study of IPX066 in Advanced Parkinson’s disease

Issued: London UK, Hayward, CA

• IPX066 demonstrated statistically significant improvement over carbidopa-levodopa plus entacapone in reducing the percentage of “off time” during waking hours

GlaxoSmithKline (GSK) and Impax Pharmaceuticals, the branded products division of Impax Laboratories, Inc. (NASDAQ: IPXL) today announced top-line results of the ASCEND-PD Phase III clinical study of IPX066 versus carbidopa-levodopa plus entacapone (CLE), in patients with advanced Parkinson’s disease (PD). IPX066 is an extended release capsule formulation of carbidopa-levodopa (CD-LD) under investigation for the treatment of the motor symptoms of PD.

The primary endpoint of this double blind crossover study was the percentage of “off time” during waking hours as measured by patient diary. “Off time” is the functional state when patients’ medication effect has worn off and there is a return of the motor symptoms of PD.  Patients entered the study with a baseline “off time” of 36.1% (5.9 hours), and at the end of the randomized IPX066 treatment phase patients had “off time” of 24.0% (3.8 hours) during waking hours compared to 32.5% (5.2 hours) for CLE (p<0.0001). This represents a 33.5% decrease in percent “off time” for IPX066 from baseline vs. a 10% decrease for CLE.

“Impax Pharmaceuticals and GSK are excited to report these positive results for the ASCEND-PD trial which demonstrate an 84 minute improvement in “off time” over CLE therapy with a corresponding increase in “on time” without troublesome dyskinesiA," stated Dr. Suneel Gupta, Impax Pharmaceuticals' chief scientific officer. "Consistent with our earlier ADVANCE-PD Phase III study findings, this study also demonstrates that IPX066 provides efficacy across a range of clinically meaningful measures in advanced PD.  We are also pleased that the secondary endpoints supported the conclusion from the primary endpoint.”

During the double blind crossover period of this trial the adverse event (AE) rate for IPX066 was 20% compared to 14% for CLE. After randomisation two serious treatment-emergent adverse events were reported with both occurring on IPX066 therapy (sciatica and dehydration) and none on CLE. The most common AEs reported for IPX066 included: insomnia, confusional state, and dyskinesia (each event was reported by 3 subjects). The most common AE reported for CLE was: fall (reported by 2 patients on CLE).

Impax plans to submit these data as part of its New Drug Application (NDA) for IPX066 to the FDA, which is planned for the fourth quarter of 2011.  GSK plans to file the Marketing Authorisation Application for IPX066 in the European Union in 2012.  

Full results from the ASCEND-PD study will be presented at an upcoming scientific meeting.

About the ASCEND-PD study
The ASCEND-PD study is a randomised, double-blind 2-treatment, 2-week crossover study of IPX066 and CLE (a combination treatment of carbidopa-levodopa and entacapone, an enzyme inhibitor of levodopa breakdown), and one of three Phase III studies of IPX066.  Study subjects taking a stable dose of CLE were converted to IPX066 over a six-week period, then randomised to one of the two treatments (IPX066 or CLE) for two weeks and then crossed over to the other treatment for an additional two weeks after a one-week washout with IPX066. The study enrolled 110 subjects, with 91 subjects entering the randomised comparative phase of the study. A total of 84 subjects completed the randomised double-blind comparative phase of the study. Following the comparative phase, subjects were enrolled into a six-month open-label extension study.

About IPX066
IPX066 is an investigational extended release capsule formulation of CD-LD which is intended to maintain consistent plasma concentration of levodopa for a longer duration versus immediate release levodopa, which may have an impact on fluctuations in clinical response. It is not approved or licensed anywhere in the world.

Results from the pivotal phase III studies of IPX066, ADVANCE-PD (in advanced PD) and APEX-PD (in early PD) have previously been announced and presented at the American Academy of Neurology and International Congress of Parkinson’s Disease and Movement Disorders Conference in April and June 2011, respectively. Open-label extension studies for subjects who have completed the ADVANCE-PD and APEX-PD are ongoing.

About the Impax GSK collaboration
GSK and Impax Pharmaceuticals announced an agreement for the development and commercialisation of IPX066 in December 2010. Under the terms of the agreement, GSK received an exclusive license to register and commercialise IPX066 throughout the world except in the U.S. and Taiwan. 

About Parkinson’s Disease
Parkinson’s disease is a chronic neurodegenerative movement disorder affecting over three million people in the US, Europe, and Japan.

GlaxoSmithKline – one of the world’s leading research-based pharmaceutical and healthcare companies – is committed to improving the quality of human life by enabling people to do more, feel better and live longer.  For further information please visit www.gsk.com 

GlaxoSmithKline Cautionary statement regarding forward-looking statements
Under the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995, GSK cautions investors that any forward-looking statements or projections made by GSK, including those made in this announcement, are subject to risks and uncertainties that may cause actual results to differ materially from those projected. Factors that may affect GSK' s operations are described under 'Risk Factors' in the 'Business Review' in the company' s Annual Report on Form 20-F for 2010.

IMPAX safe harbor statement under the Private Securities Litigation Reform Act of 1995:
To the extent any statements made in this news release contain information that is not historical, these statements are forward-looking in nature and express the beliefs and expectations of management. Such statements are based on current expectations and involve a number of known and unknown risks and uncertainties that could cause the Company’s future results, performance or achievements to differ significantly from the results, performance or achievements expressed or implied by such forward-looking statements. Such risks and uncertainties include, but are not limited to, the effect of current economic conditions on the Company’s industry, business, financial position and results of operations, the ability to maintain an effective system of internal control over financial reporting, fluctuations in revenues and operating income, the ability to successfully develop and commercialize pharmaceutical products, reductions or loss of business with any significant customer or a reduction in sales of any significant product, the impact of competition, the ability to sustain profitability and positive cash flows, any delays or unanticipated expenses in connection with the operation of the Taiwan facility, the effect of foreign economic, political, legal and other risks on operations abroad, the uncertainty of patent litigation, consumer acceptance and demand for new pharmaceutical products, the difficulty of predicting Food and Drug Administration filings and approvals, the inexperience of the Company in conducting clinical trials and submitting new drug applications, the ability to successfully conduct clinical trials, reliance on alliance and collaboration agreements, the availability of raw materials, the ability to comply with legal and regulatory requirements governing the pharmaceutical and healthcare industries, the regulatory environment, the ability to protect the Company’s intellectual property, exposure to product liability claims and other risks described in the Company’s periodic reports filed with the Securities and Exchange Commission. Forward-looking statements speak only as to the date on which they are made, and Impax undertakes no obligation to update publicly or revise any forward-looking statement, regardless of whether new information becomes available, future developments occur or otherwise.