Adamas Announces Positive Top-Line Phase 3 Results of ADS-5102 for the Treatment of Levodopa-induced Dyskinesia in Patients With Parkinson’s Disease
Conference Call and Webcast Today at 8:00 a.m. Eastern Time (5:00 a.m. Pacific Time)
EMERYVILLE, Calif., Dec. 23, 2015 -- Adamas Pharmaceuticals, Inc. (ADMS) today announced that its Phase 3 EASE LID clinical trial evaluating the company’s investigational compound ADS-5102 (amantadine HCl) extended-release capsules for the treatment of levodopa-induced dyskinesia (LID) associated with Parkinson’s disease met its primary endpoint. Results from this randomized, placebo-controlled study showed a statistically significant reduction (p = 0.0009) in LID at 12 weeks for patients who received ADS-5102 versus placebo as assessed by the Unified Dyskinesia Rating Scale (UDysRS). This represents a 23 percent reduction in LID for ADS-5102-treated patients compared to placebo. The reduction in LID was maintained at 24 weeks (p = 0.0008), a key secondary analysis. The company plans to present comprehensive data at an upcoming scientific conference.
“We are very pleased with these top-line results that confirm and extend the positive findings from our earlier randomized, placebo-controlled study,” stated Gregory T. Went, Ph.D., Chairman and Chief Executive Officer of Adamas Pharmaceuticals, Inc. “Parkinson’s disease patients have no approved medicine for this potentially serious complication of levodopa therapy. With these data in hand, we look forward to talking with the FDA about our planned NDA submission for ADS-5102."
In this study, there were four additional key secondary analyses based on patient diary data. All achieved statistical significance. Notably, at week 12, ADS-5102 significantly increased ON time without troublesome dyskinesia by 2.7 hours versus placebo and reduced OFF time by 0.9 hours. These effects were maintained at week 24.
“These data are impressive and suggest that ADS-5102 has a clinically relevant effect on dyskinesia,” said Rajesh Pahwa, M.D., Laverne & Joyce Rider Professor of Neurology, Director of the Parkinson’s Disease and Movement Disorder Center at the Kansas University Medical Center. “As a member of the Parkinson’s community, I welcome a drug for treating levodopa-induced dyskinesia that does not worsen the motor features of Parkinson’s disease.”
Efficacy analyses were based on a modified intent to treat (mITT) population of 121 moderate to advanced Parkinson’s disease patients with LID. The treatment groups were similar with respect to baseline demographics and Parkinson’s disease related medical history.
The reported adverse events associated with ADS-5102 were consistent with the known safety profile of amantadine as well as the safety results from our earlier placebo-controlled trial. The most common adverse events (occurring in greater than five percent of ADS-5102-treated patients) were: hallucinations, peripheral edema, dizziness, dry mouth, constipation, falls, urinary tract infections, anxiety, contusion, livedo reticularis, abnormal dreams, depression and headaches. Four subjects discontinued treatment due to adverse events in the placebo group versus 13 in the ADS-5102 group. There were 17 severe adverse events, four in the placebo group and 13 in the ADS-5102 group. Of these severe adverse events, one event in the placebo group and three events in the ADS-5102 group were assessed to be study drug related. There were 10 serious adverse events, three in the placebo group and seven in the ADS-5102 group, none of which were assessed to be study drug related.
About EASE LID
The Phase 3 EASE LID study was a multi-center, randomized, double-blind, placebo-controlled study designed to evaluate the safety and efficacy of 340 mg of ADS-5102 dosed once daily at bedtime for 24 weeks in patients with LID associated with Parkinson’s disease. The study's primary efficacy analysis measured the reduction in LID over 12 weeks as assessed by the Unified Dyskinesia Rating Scale (UDysRS). The key secondary efficacy outcome measures were a reduction in LID over 24 weeks as assessed by the UDysRS and changes in a standardized Parkinson’s disease diary, including ON time without troublesome dyskinesia and OFF time at weeks 12 and 24. Additional secondary efficacy outcome measures included overall Parkinson’s disease clinical status as assessed by the MDS-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) and the Clinicians Global Impression of Change.
Conference Call and Webcast Today, December 23, at 8:00 a.m. Eastern Time (5:00 a.m. Pacific Time)
The Adamas management team will host a conference call and webcast at 8:00 a.m. ET/ 5:00 a.m. PT on Wednesday, December 23 to discuss the study results. Interested parties may access the webcast on the Adamas website at http://ir.adamaspharma.com/events.cfm, or by dialing 844-215-3280 (domestic) or 484-747-6383 (international) and referencing conference ID 15542042. A replay of the call will be available on the Adamas website later in the day. The replay will be available for approximately one month following the call.
Ongoing Phase 3 Studies
In addition to the EASE LID study discussed in this release, the company is conducting EASE LID 3, a Phase 3, 13-week, multi-center, randomized, double-blind, placebo-controlled study designed to 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 from baseline to week 12. The trial completed enrollment of 77 patients in December 2015. Adamas is also conducting EASE LID 2, an open-label safety study, which is open to patients from EASED, EASE LID, EASE LID 3 and LID patients who have undergone deep brain stimulation.
Parkinson's Disease and Levodopa-induced Dyskinesia
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 levodopa-induced dyskinesia (LID), a condition characterized by involuntary movements without purpose. As Parkinson's disease advances, the symptoms of LID often worsen in frequency and severity. Eventually the total time that a patient spends ON with LID can become a significant portion of his or her day.
Adamas’ most advanced wholly owned product candidate is ADS-5102 (amantadine HCl), an extended-release version of amantadine that is intended for once daily administration at bedtime. ADS-5102 is designed to improve upon the pharmacokinetic (PK) profile of immediate-release amantadine, with the aim of enhancing efficacy without compromising the known tolerability profile. In PK studies, ADS-5102 has been shown to achieve high plasma amantadine concentrations in the early morning that are sustained throughout the afternoon and are lower in the evening.
About Adamas Pharmaceuticals
Adamas Pharmaceuticals, Inc. is driven to improve the lives of those affected by chronic disorders of the central nervous system. The company seeks to achieve this by modifying the pharmacokinetic profiles of approved drugs to create novel therapeutics for use alone and in fixed-dose combination products. Adamas is currently developing ADS-5102, its lead wholly owned product candidate, for the treatment of levodopa-induced dyskinesia associated with Parkinson's disease and for the treatment of major symptoms associated with multiple sclerosis in patients with walking impairment. The company's portfolio also includes Namzaric™ and Namenda XR®, two approved products with Forest Laboratories Holdings Limited, an indirect wholly owned subsidiary of Allergan plc. Forest is responsible for marketing both products in the United States under an exclusive license from Adamas. For more information, please visit www.adamaspharma.com.
Namzaric™ is a trademark of Merz Pharma GmbH & Co. KGaA.
Namenda XR® is a registered trademark 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 such as expectations regarding the potential for ADS-5102 in levodopa-induced dyskinesia and other symptoms of Parkinson’s disease, regulatory progress and interactions with the FDA. 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 the FDA’s interpretation and review of the ADS-5102 data and program, and ongoing research, clinical and development activities of ADS-5102, as well as risks relating to Adamas’ business in general, see Adamas’ Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission on November 12, 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.
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