EMERYVILLE, Calif., June 22, 2016 (GLOBE NEWSWIRE) -- Adamas Pharmaceuticals, Inc. (Nasdaq:ADMS) today announced additional data from its Phase 3 clinical program of ADS-5102 (amantadine HCl) extended-release capsules for the treatment of levodopa-induced dyskinesia (LID) associated with Parkinson’s disease (PD) at the 20th Annual International Congress of Parkinson’s and Movement Disorders in Berlin, Germany. Data was presented from two trials -- EASE LID and EASE LID 2 -- by Rajesh Pahwa, M.D., a recognized expert in PD and LID. Levodopa-induced dyskinesia, which is a condition characterized by involuntary movements without purpose, can become severely disabling, rendering people with Parkinson’s disease unable to perform routine daily tasks.
“This growing body of data supports the potential use of ADS-5102 for the treatment of LID,” stated Rajesh Pahwa, M.D., Laverne & Joyce Rider Professor of Neurology and Director of the Parkinson's Disease and Movement Disorder Center at the University of Kansas Medical Center. “In addition to seeing improvement across all subgroups in the Phase 3 EASE LID study, we observed in EASE LID 2, Adamas’ open-label safety study, that the reduction in motor complications associated with ADS-5102 was maintained for up to 41 weeks based on the first interim analysis. The tolerability of ADS-5102 is also encouraging when considering the age and disabilities normally observed in the Parkinson’s population.”
“We believe the data set we have amassed, and continue to build, from our Phase 3 program of ADS-5102 for dyskinesia associated with Parkinson’s disease serves as a solid foundation for the new drug application that we plan to submit to the FDA this year,” said Rajiv Patni, M.D., Adamas’ Chief Medical Officer. “If approved, ADS-5102 could be the first medicine for LID, representing a major step forward in the treatment of this debilitating condition.”
ADS-5102 Extended-Release Capsules Reduced Levodopa-Induced Dyskinesia in the Phase 3 EASE LID Study; Abstract 2012 – Featured in ‘Berlin’s Top Abstract’ Display and Guided Poster Tour
Analysis of data from EASE LID revealed a positive treatment effect for the ADS-5102-treated patients across all subgroups including: age, gender, renal function, and severity of motor complications (as measured at baseline). As previously reported, the Phase 3 EASE LID study met its primary endpoint with a highly statistically significant reduction in dyskinesia at week 12. The study also met all five pre-specified key secondary endpoints. Improvement in LID was observed at the first post-baseline assessment at week 2 and durable throughout the study (week 24 observation). The efficacy of ADS-5102 was achieved without worsening the underlying PD. ADS-5102 was generally well tolerated, and the types of adverse events (AEs) reported were consistent with the known safety profile of amantadine.
Interim Results of a Long-term Open-label Safety Study of ADS-5102 Extended-Release Capsules for Treatment of Levodopa-Induced Dyskinesia (EASE LID 2 Study); Abstract LBA 07
The EASE LID 2 study is an open-label long-term safety study of ADS-5102. Enrollment was open to individuals who had completed prior participation in Adamas-sponsored LID studies, as well as individuals who, despite having undergone deep brain stimulation, had LID. The most common AEs in any group that occurred in at least five percent of patients included: falls, visual hallucinations, abnormal dreams, dizziness, peripheral edema, constipation and dry mouth. The types of AEs reported in this study were consistent with the known safety profile of amantadine and previous Adamas-sponsored randomized studies. Of the patients from EASE LID who were naïve to ADS-5102 prior to this study, there were six (18%) who discontinued treatment due to AEs. This is comparable to that seen in previous controlled studies. For patients who continued ADS-5102 treatment from the prior 6-month controlled trial (EASE LID), there was one subject who discontinued due to AEs.
This study, although designed to characterize the long-term safety and tolerability of ADS-5102, also generated non-controlled efficacy data. In the study, previously treated patients maintained their ADS-5102 reduction in motor complications for up to 41 weeks (as of the time of the first interim analysis). Additionally, patients who were naïve to ADS-5102 prior to this study also experienced a reduction in motor complications as observed at their first post-baseline assessment. These effects were achieved without compromising the underlying control of PD symptoms.
ADS-5102 Phase 3 Program Overview
Adamas’ Phase 3 clinical program of ADS-5102 for the treatment of LID comprises three placebo-controlled trials: EASED, EASE LID and EASE LID 3. These trials enrolled a total of 286 patients, of which 122 patients received a 340 mg dose of ADS-5102 once daily before bedtime for a prespecified period of time. In all three trials, changes in LID versus placebo were assessed by the Unified Dyskinesia Rating Scale (UDysRS): week 8 (EASED), week 12 and week 24 (EASE LID) and week 12 (EASE LID 3). EASE LID 2, an open-label safety study open to patients from EASED, EASE LID and EASE LID 3 and to LID patients who have undergone deep brain stimulation, is ongoing.
About ADS-5102
Adamas' most advanced wholly-owned product candidate is ADS-5102 (amantadine HCl) 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.
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). 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.
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 is also evaluating ADS-4101, an extended-release version of an FDA-approved single-agent compound for the treatment of epilepsy. In addition, under a license agreement with Forest Laboratories Holdings Limited, an indirect wholly-owned subsidiary of Allergan plc., the company is eligible to receive royalties from Forest on sales of Namenda XR® and Namzaric™ beginning in June of 2018 and May of 2020, respectively. 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.
The statements contained in this press release that are not historical fact, including those regarding results from Adamas’ randomized Phase 3 EASE LID trial, and its EASE LID 2 open-label study and statements regarding the potential for ADS-5102 for the treatment of LID, timing of the NDA submission, possible FDA approval and potential for ADS-5102 to become the first treatment for LID, are “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. For a 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, ongoing research, clinical and development activities of ADS-5102, the regulatory and competitive environment, as well as risks relating to Adamas’ business in general, see Adamas’ 10-Q filed with the Securities and Exchange Commission on May 10, 2016. 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.