Adamas Announces Additional Findings From Its Phase 2/3 Trial of ADS-5102 for the Treatment of Levodopa-induced Dyskinesia (LID) Associated with Parkinson's Disease
Analysis of Patient Diaries Indicates Treatment with ADS-5102 Increases ON Time Without Troublesome LID Throughout Day
EMERYVILLE, Calif., June 15, 2015 -- Adamas Pharmaceuticals, Inc. (ADMS) today announced additional findings from its Phase 2/3 study (EASED) evaluating ADS-5102 for the treatment of levodopa-induced dyskinesia (LID), a movement disorder associated with the treatment of Parkinson's disease. Patient diary data were analyzed to characterize the time course of troublesome LID and other Parkinson's disease states during waking hours, synchronized to the patients' wake-up times as well as to elucidate the impact of treatment with ADS-5102. These data showed that troublesome LID was reported throughout the day. After eight weeks of treatment, the majority of ADS-5102-treated patients reported an increase in the quality of ON time by increasing ON time without troublesome LID throughout the morning, afternoon and evening. In contrast, placebo-treated patients reported little change in their dyskinesia. These results (Abstract # 329) are being presented at the 19th International Congress of Parkinson's Disease and Movement Disorders in San Diego, California.
In this post hoc analysis, to better understand motor complications experienced throughout waking hours, a data set was assembled synchronized according to each patient's wake-up time. This analysis included data from patient diaries (n= 62) at baseline and after eight weeks of treatment with either ADS-5102 (n=42, all doses) or placebo (n=20). This analysis revealed that prior to treatment (baseline), study participants experienced, over the course of the day, a complex and dynamic pattern of Parkinson's disease states, including ON time with and without troublesome LID and OFF time. After eight weeks of placebo treatment, there was little change in this pattern. In contrast, the majority of ADS-5102-treated individuals were able to maintain ON time without troublesome LID throughout the waking day, for at least 14 hours after waking up. ADS-5102 was generally well tolerated and reported adverse event terms were consistent with Parkinson's disease and the known amantadine safety profile.
"This new insight from the EASED Phase 2/3 study further suggests the potential role ADS-5102 may have in helping individuals living with Parkinson's disease reduce the burden of troublesome dyskinesia throughout their day," stated Natalie McClure, Ph.D., Senior Vice President of Product Development at Adamas Pharmaceuticals, Inc. "We look forward to the results of our ongoing confirmatory Phase 3 trials evaluating the safety and efficacy of ADS-5102 for the treatment of levodopa-induced dyskinesia."
The EASED study, a randomized, placebo-controlled, multi-center study, evaluated patients with Parkinson's disease experiencing troublesome LID. Patients were randomized to receive placebo or to one of three dose levels of ADS-5102. As previously reported, ADS-5102 significantly reduced LID as measured by change in UDysRS (a tool that assesses the disability and impairment of LID in Parkinson's disease) over eight weeks versus placebo (primary endpoint, p=0.005 for the 340 mg dose group). Data also suggested that ADS-5102 was generally well tolerated and reported adverse event terms were consistent with Parkinson's disease and the known amantadine safety profile.
Comprehensive Registration Program
Adamas has three ongoing clinical trials for the treatment of LID in individuals with Parkinson's disease:
EASE LID, a Phase 3 study, which is planned to enroll approximately 130 patients. The 26-week multi-center, randomized, double-blind, placebo-controlled study will assess the efficacy of a 340 mg dose of ADS-5102 administered once daily at bedtime. The primary endpoint of EASE LID is a reduction in dyskinesia assessed by changes in UDysRS with a key secondary endpoint being the patient diaries.
EASE LID 2, a Phase 3 open-label safety study of ADS-5102 in Parkinson's disease patients with LID.
EASE LID 3, a Phase 3 study, which is estimated to enroll approximately 70 patients. The 13-week multi-center, randomized, double-blind, placebo-controlled study will assess the efficacy of a 340 mg dose of ADS-5102 administered once daily at bedtime. The primary endpoint of EASE LID 3 is a reduction in dyskinesia assessed by changes in UDysRS with a key secondary endpoint being the patient diaries.
Parkinson's Disease and Levodopa-induced Dyskinesia (LID)
Parkinson's disease is a chronic, progressive motor disorder that causes a variety of symptoms, such as tremors, rigidity, slowed movements and postural instability. The most commonly prescribed treatments for Parkinson's disease are levodopa-based therapies. In the body, levodopa is converted to dopamine to replace the dopamine loss caused by the disease. Patients initially receive relief from symptoms of Parkinson's disease for much of the day. This period of relief is known as ON time. As the effects of levodopa wear off, the symptoms of Parkinson's disease return. This is known as OFF time.
As Parkinson's disease progresses, most patients require increasing doses of levodopa to achieve equivalent therapeutic benefit. Patients may also experience symptoms of their disease upon waking, prior to the first dose of levodopa taking effect. Over time many patients will suffer from LID, a condition characterized by involuntary movements without purpose. LID can become severely disabling, rendering patients unable to perform routine daily tasks. As Parkinson's disease advances, the symptoms of LID worsen in frequency and severity. Eventually the total time that a patient spends ON with LID can become a majority of his or her day.
Adamas' most advanced wholly owned product candidate is ADS-5102 (amantadine HCl), a high-dose, extended-release version of amantadine that is administered once daily at bedtime. Adamas is initially developing ADS-5102 for the treatment of levodopa-induced dyskinesia, or LID, in patients with Parkinson's disease. There are no approved drugs for the treatment of LID in the United States or Europe. In addition, Adamas is exploring the utility of ADS-5102 for the treatment of major symptoms associated with multiple sclerosis in patients with gait impairment.
About Adamas Pharmaceuticals
Adamas Pharmaceuticals, Inc. is a specialty pharmaceutical company driven to improve the lives of those affected by chronic disorders of the central nervous system. The company achieves this by modifying the pharmacokinetic profiles of approved drugs to create novel therapeutics for use alone or in fixed-dose combination products. Adamas is currently developing its lead wholly owned product candidate, ADS-5102, for a complication associated with the treatment of Parkinson's disease known as levodopa-induced dyskinesia, or LID, and is evaluating other potential applications, including for the treatment of symptoms associated with multiple sclerosis in patients with gait impairment. The company's portfolio also includes two approved products with Forest Laboratories Holdings Limited (a subsidiary of Actavis plc), Namzaric(TM) and Namenda XR(R). Forest markets both products in the United States under an exclusive license from Adamas. For more information, please visit www.adamaspharma.com.
Namenda XR(R) is a registered trademark of Merz Pharma GmbH & Co. KGaA.
Namzaric(TM) and its design are trademarks of Merz Pharma GmbH & Co. KGaA.
Statements contained in this press release regarding matters that are not historical facts are "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995, including but not limited to, statements contained in this press release include expectations regarding the potential for ADS-5102 in levodopa-induced dyskinesia and other indications, and the progress associated with our clinical trials. Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. Words such as "may," "will," "expect," "anticipate," "estimate," "intend," and similar expressions (as well as other words or expressions referencing future events, conditions, or circumstances) are intended to identify forward-looking statements. For a further description of the risks and uncertainties that could cause actual results to differ from those expressed in forward-looking statements, including risks relating to research, clinical and development activities of ADS-5102, challenges associated with clinical trials including delays in enrollment, as well as risks relating to Adamas' business in general, see Adamas' Annual Report on Form 10-Q filed with the Securities and Exchange Commission on May 13, 2015. Investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date of this release. Adamas undertakes no obligation to update any forward-looking statement in this press release.